BACKGROUND AND HYPOTHESIS:Iohexol and 99mTc-DTPA are commonly used exogenous filtration markers for determining measured glomerular filtration rate (mGFR). Traditional intravenous sampling is time-consuming and often inconvenient in clinical practice, whereas dried blood spot (DBS) sampling is a promising alternative. This study used population pharmacokinetic modeling (popPK) and traditional performance statistics to investigate whether intravenous and DBS sampling can be used interchangeably for measuring GFR in older medical patients with low appetite. METHODS:Older patients aged ≥65 years with poor appetite, defined as a Simplified Nutritional Appetite Questionnaire (SNAQ) score ≤14, received intravenous administration of iohexol and 99mTc-DTPA, followed by sampling over 4-8 hours intravenously (for both tracers) and by DBS (for iohexol). Gentamicin 5 mg/kg was used as a model drug and administered intravenously to all patients, followed by plasma sampling over 22 hours. Employing a previously developed gentamicin popPK model, model fit improvement for each mGFR method was evaluated by reduction in objective function value (OFV) and inter-individual variability (IIV) when including mGFR as a covariate on clearance. Performance of each method relative to intravenous iohexol sampling was also evaluated by bias (median difference) and P15 (percentage of values within 15%). RESULTS:51 older patients (51% male, aged 67-96) were included. All three mGFR methods improved model fit when implemented as covariates on gentamicin clearance in popPK models (-ΔOFV = 115.6-137.6). The improvements were greater when mGFR was expressed in mL/min, rather than mL/min/1.73 m2. Compared to intravenous sampling of iohexol, DBS sampling of iohexol performed better (bias [95% CI] = 2 [0-3] mL/min, P15 = 98% [94.1%-100%]) than intravenous sampling of 99mTc-DTPA (bias = 4 [3-5] mL/min, P15 = 78.4% [66.7%-88.2%]). CONCLUSIONS:Compared to intravenous sampling of iohexol or 99mTc-DTPA, DBS sampling of iohexol yielded similar improvements to model fit when incorporated as a covariate on gentamicin clearance in a popPK model.

ABSTRACT Background and hypothesis Iohexol and 99m-technetium-diethylenetriaminepentaacid (99mTc-DTPA) are commonly used exogenous filtration markers for determining measured glomerular filtration rate (mGFR). Traditional intravenous sampling is time-consuming and often inconvenient in clinical practice, whereas dried blood spot (DBS) sampling is a promising alternative. This study used population pharmacokinetic (popPK) modelling and traditional performance statistics to investigate whether intravenous and DBS sampling can be used interchangeably for measuring GFR in older medical patients with low appetite. Methods Older patients aged ≥65 years with poor appetite, defined as a Simplified Nutritional Appetite Questionnaire score ≤14, received intravenous administration of iohexol and 99mTc-DTPA, followed by sampling over 4–8 h intravenously (for both tracers) and by DBS (for iohexol). Gentamicin 5 mg/kg was used as a model drug and administered intravenously to all patients, followed by plasma sampling over 22 h. Employing a previously developed gentamicin popPK model, model fit improvement for each mGFR method was evaluated by reduction in objective function value (OFV) and inter-individual variability when including mGFR as a covariate on clearance. Performance of each method relative to intravenous iohexol sampling was also evaluated by bias (median difference) and P15 (percentage of values within 15%). Results In this study, 51 older patients (51% male, aged 67–96) were included. All three mGFR methods improved model fit when implemented as covariates on gentamicin clearance in popPK models (−ΔOFV = 115.6–137.6). The improvements were greater when mGFR was expressed in ml/min, rather than ml/min/1.73 m2. Compared to intravenous sampling of iohexol, DBS sampling of iohexol performed better (bias [95% confidence interval] = 2 [0–3] ml/min, P15 = 98% [94.1%–100%]) than intravenous sampling of 99mTc-DTPA (bias = 4 [3–5] ml/min, P15 = 78.4% [66.7%–88.2%]). Conclusions Compared to intravenous sampling of iohexol or 99mTc-DTPA, DBS sampling of iohexol yielded similar improvements to model fit when incorporated as a covariate on gentamicin clearance in a popPK model.

Introduction Accurate assessment of kidney function is essential for dosing renally eliminated drugs such as gentamicin. However, creatinine-based estimated glomerular filtration rate (eGFR) equations may be inaccurate in older adults because creatinine concentrations are influenced by non-renal factors, including reduced muscle mass and frailty. This study investigated whether measured GFR (mGFR) and ten different eGFR equations improve the modeling of gentamicin renal clearance, used as a model compound for renally eliminated drugs, when included as covariates in a population pharmacokinetic (popPK) model of older medical patients with poor appetite. Methods This prospective diagnostic accuracy and population pharmacokinetic study evaluated mGFR determined by 99mTc-DTPA plasma clearance and ten eGFR equations based on plasma creatinine, cystatin C, β2-microglobulin, and/or β-trace protein. Poor appetite was assessed using the Simplified Nutritional Appetite Questionnaire (SNAQ). Plasma gentamicin concentrations were measured over 22 hours following a single intravenous dose of 5 mg/kg. Gentamicin concentration–time profiles were analyzed using nonlinear mixed-effects modeling. Improvement in model performance was assessed by changes in objective function value (OFV) and interindividual variability (IIV) in clearance. Results Fifty-two older medical patients with poor appetite (median age 79.5 [IQR 73.0–84.3] years, 56% female, median SNAQ score 12 [IQR 11–13]) were included. mGFR expressed in mL/min provided the greatest improvement in model fit when included as a covariate on gentamicin clearance (−ΔOFV = 115.00). Among eGFR equations, combined creatinine–cystatin C equations expressed in mL/min yielded the best performance (−ΔOFV = 72.58–77.11), whereas creatinine-only equations showed the poorest improvement (−ΔOFV <63.69). Overall, absolute GFR estimates performed better than body surface area-indexed estimates. Conclusions Creatinine-only eGFR equations may be suboptimal proxies for gentamicin clearance in this patient population. If measuring GFR is unfeasible, estimating GFR based on a combination of creatinine and cystatin C is the best alternative.

Accurate glomerular filtration rate (GFR) estimation is crucial for diagnosing kidney disease and prescribing renal risk medications [1-3]. In clinical practice, estimated GFR (eGFR) is typically determined by plasma creatinine levels adjusted for age and sex (eGFRcre) [4]. However, creatinine is an imperfect metric of GFR, particularly in older (age ≥ 65 years) hospitalized patients, due to age-related changes in non-GFR factors such as muscle mass and nutritional status that affect creatinine level [5]. The addition of cystatin C to creatinine (eGFRcomb) improves the accuracy of GFR estimates for older hospitalized patients, but there remains a large and unpredictable margin of error compared with measured GFR (mGFR)

Background: Patients with cirrhosis often develop hyperdynamic circulation with increased cardiac output, heart rate, and redistribution of the circulating volume with expanded plasma volume (PV). PV determination is part of the evaluation of patients with cirrhosis, but gold-standard methods are invasive, expensive, and time-consuming. Therefore, other estimations of PV would be preferable, and the aim of this study was therefore to study if PV, as assessed by a simplified algorithm based on hematocrit and weight, can replace the gold-standard method. Methods: We included 328 patients with cirrhosis who had their PV assessed by the indicator dilution technique as the gold-standard method (PVI-125). Actual PV was estimated as PVa = (1 − hematocrit)·(a + (b·body weight)). Ideal PV was estimated as PVi = c · body weight, where a, b, and c are constants. Results: PVI-125, PVa, and PVi were 3.99 ± 1.01, 3.09 ± 0.54, and 3.01 ± 0.65 (Mean ± SD), respectively. Although PVI-125 correlated significantly with PVa (r = 0.72, p < 0.001), a Bland–Altman plot revealed wide limits of confidence. Conclusions: The use of simplified algorithms does not sufficiently estimate PV and cannot replace the indicator dilution technique.

In their editorial, Grubb et al1Grubb A.O. Magnusson M. Christensson A. Etiologic and diagnostic implications of morbidity and mortality associations when cystatin C–based estimated GFR is lower than creatinine-based estimated GFR.Am J Kidney Dis. 2023; 82: 509-511https://doi.org/10.1053/j.ajkd.2023.08.001Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar examine differences between cystatin C– and creatinine-based estimated glomerular filtration rate (eGFRcys and eGFRcr, respectively). An eGFRcys:eGFRcr ratio <0.7 occurs in 0.3%-36% of patients2Malmgren L. Öberg C. den Bakker E. et al.The complexity of kidney disease and diagnosing it – cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.J Intern Med. 2023; 293: 293-308https://doi.org/10.1111/joim.13589Crossref PubMed Scopus (23) Google Scholar (depending on the population) and is associated with worse health outcomes. The authors demonstrate how this ratio can be influenced both by nonrenal factors and by selective hypofiltration of cystatin C. However, most countries do not routinely measure cystatin C, limiting the application of this important distinction. Our own research in Denmark focuses on the utility of cystatin C for older adults with multimorbidity. We recently completed a study investigating the performance of eGFRcr, eGFRcys, and a combined estimate (eGFRcr-cys) among older adults at Hvidovre Hospital in Copenhagen, Denmark.3Iversen E. Bengaard A.K. Leegaard Andersen A. et al.Performance of panel-estimated GFR among hospitalized older adults.Am J Kidney Dis. 2023; 82: 715-724https://doi.org/10.1053/j.ajkd.2023.05.004Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Patients with prior amputation, use of an immunosuppressive medication, or acute kidney injury were excluded. Inspired by Grubb et al, we present data here showing the prevalence and clinical characteristics of patients with an eGFRcys:eGFRcr ratio <0.7. In total, we collected data for 106 patients with a mean age of 79.0 years and measured GFR of 62.7 mL/min/1.73 m2 (Table 1). Compared to patients with an eGFRcys:eGFRcr ratio ≥0.7, those with an eGFRcys:eGFRcr ratio <0.7 (36% of all patients) had lower kidney function, higher rates of malnutrition, greater established comorbidity (eg, cardiovascular disease, cerebrovascular disease, and diabetes mellitus), and higher levels of soluble urokinase plasminogen activator receptor, a proxy for overall disease burden.4Rasmussen L.J.H. Petersen J.E.V. Eugen-Olsen J. Soluble urokinase plasminogen activator receptor (suPAR) as a biomarker of systemic chronic inflammation.Front Immunol. 2021; 12780641https://doi.org/10.3389/fimmu.2021.780641Crossref Scopus (68) Google Scholar In both patient groups, eGFRcr-cys performed best relative to measured GFR. Smaller numbers in the group with eGFRcys:eGFRcr ratio <0.7 likely contribute to the poorer performance matrix. Further research is needed to determine whether discrepancies between eGFRcys and eGFRcr are due to nonrenal factors affecting filtration marker concentration or some underlying pathophysiology causing selective hypofiltration.5Quiroga B. Ortiz A. Díez J. Selective glomerular hypofiltration syndrome.Nephrol Dial Transplant. 2023; 39: 10-17https://doi.org/10.1093/ndt/gfad145Crossref PubMed Scopus (6) Google ScholarTable 1Patient Characteristics and Estimated Glomerular Filtration Rate Performance Relative to Measured Glomerular Filtration Rate, Stratified by Groups Based on eGFRcys:eGFRcr RatioAll PatientseGFRcys:eGFRcr Ratio≥0.7<0.7Patient characteristicsNumber106 (100%)68 (64%)38 (36%)Age (years)79.0 ± 7.278.2 ± 6.180.3 ± 8.8Sex (female)61 (58%)38 (56%)23 (61%)Body mass index (kg/m2)27.0 ± 6.526.5 ± 5.428.0 ± 8.2 mGFR (mL/min/1.73 m2)62.7 ± 19.866.5 ± 19.755.9 ± 18.3suPAR (ng/mL)5.08 ± 2.574.77 ± 2.855.64 ± 1.86Nutritional status No malnutrition38 (36%)29 (43%)9 (24%) Malnutrition68 (64%)39 (57%)29 (76%)Comorbidities Hypertension52 (49%)34 (50%)18 (47%) Pulmonary disease43 (41%)25 (37%)18 (47%) Cardiovascular disease35 (33%)20 (29%)15 (39%) Diabetes mellitus20 (19%)11 (16%)9 (24%) Cerebrovascular disease12 (11%)6 (9%)6 (16%)Performance metricseGFRcr Bias+2.6 (–1.3 to +4.7)–2.2 (–4.1 to +0.6)+6.0 (+4.9 to +10.2) P3092% (86%-96%)97% (93%-100%)82% (68%-92%)eGFRcys Bias–11.2 (–12.9 to –9.8)–9.8 (–11.5 to –7.3)–15.1 (–21.5 to –10.9) P3078% (71%-86%)93% (85%-99%)53% (37%-68%)eGFRcr-cys Bias–1.9 (–3.5 to –0.8)–1.1 (–3.4 to +0.4)–2.9 (–6.0 to –1.0) P3096% (93%-99%)99% (96%-100%)92% (82%-100%)Patient characteristics are presented as number (percentage) or mean ± standard deviation. Performance metrics are presented with 95% confidence intervals calculated by bootstrapping with 10,000 iterations. Measured GFR was determined by plasma clearance of 99mTc-DTPA with 4- or 5-point sampling. Malnutrition was defined as a score of ≤11 on a Mini Nutritional Assessment Short-Form. Estimated GFR was calculated using the 2009 CKD-EPI equation (for eGFRcr), 2012 CKD-EPI equation (for eGFRcys), or 2021 CKD-EPI equation (for eGFRcr-cys). Bias is defined as the median difference between eGFR and mGFR in units of mL/min/1.73 m2, where positive values indicate overestimation and negative values indicate underestimation. P30 is defined as the percent of eGFR values within 30% of mGFR, where values closer to 100% indicate better performance. Abbreviations: CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; cr, creatinine; cys, cystatin C; eGFR, estimated glomerular filtration rate; mGFR, measured glomerular filtration rate; suPAR, soluble urokinase plasminogen activator receptor. Open table in a new tab Patient characteristics are presented as number (percentage) or mean ± standard deviation. Performance metrics are presented with 95% confidence intervals calculated by bootstrapping with 10,000 iterations. Measured GFR was determined by plasma clearance of 99mTc-DTPA with 4- or 5-point sampling. Malnutrition was defined as a score of ≤11 on a Mini Nutritional Assessment Short-Form. Estimated GFR was calculated using the 2009 CKD-EPI equation (for eGFRcr), 2012 CKD-EPI equation (for eGFRcys), or 2021 CKD-EPI equation (for eGFRcr-cys). Bias is defined as the median difference between eGFR and mGFR in units of mL/min/1.73 m2, where positive values indicate overestimation and negative values indicate underestimation. P30 is defined as the percent of eGFR values within 30% of mGFR, where values closer to 100% indicate better performance. Abbreviations: CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; cr, creatinine; cys, cystatin C; eGFR, estimated glomerular filtration rate; mGFR, measured glomerular filtration rate; suPAR, soluble urokinase plasminogen activator receptor. MBH is supported by the BRIDGE – Translational Excellence Programme (bridge.ku.dk) at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation (Grant No. NNF20SA0064340). This funder had no role in the design or content of this letter or the decision to submit this letter. OA is a named inventor on patents covering suPAR owned by Copenhagen University Hospital Amager & Hvidovre, Hvidovre, Denmark, and licensed to ViroGates A/S. MBH and EI declare that they have no relevant financial interests. The OptiNAM study was performed as part of the Clinical Academic Group (ACUTE-CAG) for Recovery Capacity, nominated by the Greater Copenhagen Health Science Partners (GCHSP). We thank all patients and staff involved in the OptiNAM trial. Received October 16, 2023. Direct editorial input from an Associate Editor and a Deputy Editor. Accepted in revised form November 20, 2023. In Reply to Cystatin C to Creatinine Ratio and Measured GFR in Hospitalized Older AdultsAmerican Journal of Kidney DiseasesVol. 83Issue 6PreviewThe study referred to by Houlind et al1 demonstrates that an abnormally low eGFRcystatin C:eGFRcreatinine ratio in hospitalized older Danish adults is associated not only with lower kidney function, but also with higher rates of malnutrition and greater established comorbidity. This agrees with the greater morbidity previously noted in several studies of patients with a low eGFRcystatin C:eGFRcreatinine ratio,2 which might contribute to the strong increase in mortality also noted in such patients. Full-Text PDF

The accuracy of multi-frequency (MF) bioelectrical impedance analysis (BIA) to estimate low muscle mass in older hospitalized patients remains unclear. This study aimed to describe the ability of MF-BIA to identify low muscle mass as proposed by The Global Leadership Initiative on Malnutrition (GLIM) and The European Working Group on Sarcopenia in Older People (EWGSOP-2) and examine the association between muscle mass, dehydration, malnutrition, and poor appetite in older hospitalized patients. In this prospective exploratory cohort study, low muscle mass was estimated with MF-BIA against dual-energy X-ray absorptiometry (DXA) in 42 older hospitalized adults (≥65 years). The primary variable for muscle mass was appendicular skeletal muscle mass (ASM), and secondary variables were appendicular skeletal muscle mass index (ASMI) and fat-free mass index (FFMI). Cut-off values for low muscle mass were based on recommendations by GLIM and EWGSOP-2. MF-BIA was evaluated against DXA on the ability to estimate absolute values of muscle mass by mean bias, limits of agreement (LOA), and accuracy (5% and 10% levels). Agreement between MF-BIA and DXA to identify low muscle mass was evaluated with sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). The association between muscle mass, dehydration, malnutrition, and poor appetite was visually examined with boxplots. MF-BIA overestimated absolute values of ASM with a mean bias of 0.63 kg (CI: −0.20:1.46, LOA: −4.61:5.87). Agreement between MF-BIA and DXA measures of ASM showed a sensitivity of 86%, specificity of 94%, PPV of 75% and NPV of 97%. Boxplots indicate that ASM is lower in patients with malnutrition. This was not observed in patients with poor appetite. We observed a tendency toward higher ASM in patients with dehydration. Estimation of absolute ASM values with MF-BIA should be interpreted with caution, but MF-BIA might identify low muscle mass in older hospitalized patients.

The study's aim is to compare current and new equations for estimating glomerular filtration rate (GFR) based on creatinine, cystatin C, β‐trace protein (BTP) and β2 microglobulin (B2M) among patients undergoing major amputation.

Malnutrition in older patients is linked to poor appetite. Cannabis-based medicine may have orexigenic properties in older patients, but this has to our knowledge never been investigated. In older patients, uncertainty applies to the accuracy of estimated glomerular filtration rate (eGFR) based on creatinine, which is crucial for medication prescribing. In older patients with poor appetite, the study aims (1) to assess the efficacy of Sativex® (8.1-mg delta-9-tetrahydrocannabinol [THC] and 7.5-mg cannabidiol [CBD]) to stimulate appetite and (2) to compare the performance of various GFR-estimates and measured-GFR (mGFR) for determining gentamicin clearance utilizing population pharmacokinetic (popPK) modelling methods.This study is composed of two substudies. Substudy 1 is an investigator-initiated single-center, double-blinded, randomized, placebo-controlled, superiority, cross-over study. Substudy 1 will recruit 17 older patients with poor appetite, who will also be invited to substudy 2. Substudy 2 is a single-dose pharmacokinetics study and will recruit 55 patients. Participants will receive Sativex® and placebo in substudy 1 and gentamicin with simultaneous measurements of GFR in substudy 2. The primary endpoints are as follows: Substudy 1-the difference in energy intake between Sativex® and placebo conditions; substudy 2- the accuracy of different eGFR equations compared to mGFR. The secondary endpoints include safety parameters, changes in the appetite hormones, total ghrelin and GLP-1 and subjective appetite sensations, and the creation of popPK models of THC, CBD, and gentamicin.

Background:We have recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in 23 medicated patients with Parkinson's disease (PD) compared to 23 age- and sex-matched healthy controls.Objective:To investigate in a sub-sample of the original cohort whether the observed blood flow response in SMA after oral food intake is related to a delay in gastric emptying.Methods:We studied 15 patients with PD in an "ON-medication" state with a mean disease duration of 3.9 ± 2.2 years and 15 healthy age- and sex-matched individuals. Participants underwent dynamic gastric scintigraphy 0, 30, 60, 120, 180 and 240 minutes after the intake of a standardized radiolabeled test meal. Gastric emptying was compared between groups. 14 of the 15 PD patients and 12 of the 15 healthy control subjects had previously undergone serial postprandial PC-MRI measurements. In these individuals, we tested for a relationship between gastric emptying and postprandial blood flow response in the SMA.Results:The dynamics of gastric emptying did not differ between groups (p = 0.68). There was substantial inter-subject variability of gastric emptying in PD patients and healthy participants. Only a single PD patient had delayed gastric emptying. In those participants who had undergone PC-MRI, postprandial increase in SMA blood flow was attenuated in PD compared to healthy controls as reported previously (p = 0.006). Gastric emptying did not correlate with the timing and amplitude of postprandial blood flow increase in SMA.Conclusion:Our preliminary results, obtained in a small group of early-stage PD patients who continued their usual dopamine replacement therapy, suggest that variations in gastric emptying after solid meal intake is within the normal range in the majority of cases. There is also no evidence for a tight relationship between the attenuated postprandial blood flow response in the SMA and normal variations in gastric emptying.

Costa e Silva et al. compare the performance of equations for estimated glomerular filtration rate (GFR) in patients with cancer and conclude that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations should be preferred over the Cockcroft-Gault equation. 1 Costa e Silva V.T. Gil Jr., L.A. Inker L.A. et al. A prospective cross-sectional study estimated glomerular filtration rate from creatinine and cystatin C in adults with solid tumors. Kidney Int. 2022; 101: 607-614 Google Scholar We have previously reported the clinical impact of switching between GFR equations in acutely hospitalized older patients. 2 Iversen E. Bodilsen A.C. Klausen H.H. et al. Kidney function estimates using cystatin C versus creatinine: impact of medication prescribing in acutely hospitalized elderly patients. Basic Clin Pharmacol Toxicol. 2019; 124: 466-478 Google Scholar Newly developed CKD-EPI equations without race reportedly perform even better than the CKD-EPI equations described by Costa e Silva et al., particularly in patient groups at a high risk of inaccurate estimates. 3 Inker L.A. Eneanya N.D. Coresh J. et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. 2021; 385: 1737-1749 Google Scholar Therefore, we compared the performance of these CKD-EPI equations relative to measured GFR using Tc-99m diethylene-triamine-pentaacetate (DTPA) clearance in our own high-risk cohort of older medical patients in the emergency department. 4 Andersen A.L. Houlind M.B. Nielsen R.L. et al. Optimization of Nutrition And Medication (OptiNAM) for acutely admitted older patients: protocol for a randomized single-blinded controlled trial. Trials. 2021; 22: 616 Google Scholar A prospective cross-sectional study estimated glomerular filtration rate from creatinine and cystatin C in adults with solid tumorsKidney InternationalVol. 101Issue 3PreviewCurrent guidelines recommend estimating glomerular filtration rate (eGFR) using creatinine (eGFRcr) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation as the first test for GFR evaluation, but the Cockcroft-Gault (CG) equation is still commonly used in oncology practice and clinical trials despite increasing evidence of its inaccuracy compared to measured GFR (mGFR). Guidelines recommend eGFR using cystatin C (eGFRcys) or both markers (eGFRcr-cys) as a confirmatory test, but neither was carefully evaluated in cancer patients. Full-Text PDF The authors reply:Kidney InternationalVol. 101Issue 5PreviewAs described in their letter, Iversen et al.1 assessed the performance of equations for estimated glomerular filtration rate (eGFR) using serum creatinine (eGFRcr), serum cystatin C (eGFRcys), or both (eGFRcr-cys) in 110 older medical Danish patients in the emergency department compared to measured GFR using plasma clearance of Tc-99m diethylene-triamine-pentaacetate. Like our Onco-GFR study assessing 1200 patients with cancer,2 and other studies,3 Iversen et al. demonstrated that the Cockcroft-Gault equation was the least accurate (lowest percentage of estimated GFR within 30% of the measured GFR [P30]) among eGFRcr equations and that the 2012 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcr-cys equation was more accurate (higher P30) than the 2009 CKD-EPI eGFRcr and CKD-EPI 2012 eGFRcys equations. Full-Text PDF

AbstractBackgroundInternationally, older patients (≥65 years) account for more than 40% of acute admissions. Older patients admitted to the emergency department (ED) are frequently malnourished and exposed to inappropriate medication prescribing, due in part to the inaccuracy of creatinine-based equations for estimated glomerular filtration rate (eGFR). The overall aims of this trial are to investigate: (1) the efficacy of a medication review (MED intervention) independent of nutritional status, (2) the accuracy of eGFR equations based on various biomarkers compared to measured GFR (mGFR) based on99mTechnetium–diethylenetriaminepentaacetic acid plasma clearance, and (3) the efficacy of an individualized multimodal and transitional nutritional intervention (MULTI-NUT-MED intervention) in older patients with or at risk of malnutrition in the ED.MethodsThe trial is a single-center block randomized, controlled, observer-blinded, superiority and explorative trial with two parallel groups. The population consists of 200 older patients admitted to the ED: 70 patients without malnutrition or risk of malnutrition and 130 patients with or at risk of malnutrition defined as a Mini Nutritional Assessment-Short Form score ≤11. All patients without the risk of malnutrition receive the MED intervention, which consists of a medication review by a pharmacist and geriatrician in the ED. Patients with or at risk of malnutrition receive the MULTI-NUT-MED intervention, which consists of the MED intervention in addition to, dietary counseling and individualized interventions based on the results of screening tests for dysphagia, problems with activities of daily living, low muscle strength in the lower extremities, depression, and problems with oral health. Baseline data are collected upon study inclusion, and follow-up data are collected at 8 and 16 weeks after discharge. The primary outcomes are (1) change in medication appropriateness index (MAI) score from baseline to 8 weeks after discharge, (2) accuracy of different eGFR equations compared to mGFR, and (3) change in health-related quality of life (measured with EuroQol-5D-5L) from baseline to 16 weeks after discharge.DiscussionThe trial will provide new information on strategies to optimize the treatment of malnutrition and inappropriate medication prescribing among older patients admitted to the ED.Trail registrationClinicalTrials.govNTC03741283. Retrospectively registered on 14 November 2018.

Acta PhysiologicaVolume 228, Issue 1 e13407 LETTER TO THE EDITORFree Access Comments on the Review 'Does mean arterial blood pressure scale with body mass in mammals? Effect of measurement of blood pressure' Acta Physiol (Oxf) Peter H. Sandal, Corresponding Author Peter H. Sandal Peterhsandal@gmail.com orcid.org/0000-0002-0501-2903 Department of Clinical Physiology and Nuclear Medicine, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark Department of Anaesthesiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Email: peterhsandal@gmail.comSearch for more papers by this authorMorten Damgaard, Morten Damgaard Department of Clinical Physiology and Nuclear Medicine, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, DenmarkSearch for more papers by this authorNiels H. Secher, Niels H. Secher Department of Anaesthesiology, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkSearch for more papers by this author Peter H. Sandal, Corresponding Author Peter H. Sandal Peterhsandal@gmail.com orcid.org/0000-0002-0501-2903 Department of Clinical Physiology and Nuclear Medicine, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark Department of Anaesthesiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Email: peterhsandal@gmail.comSearch for more papers by this authorMorten Damgaard, Morten Damgaard Department of Clinical Physiology and Nuclear Medicine, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, DenmarkSearch for more papers by this authorNiels H. Secher, Niels H. Secher Department of Anaesthesiology, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkSearch for more papers by this author First published: 21 October 2019 https://doi.org/10.1111/apha.13407Citations: 4AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Comments on the Review 'Does mean arterial blood pressure scale with body mass in mammals? Effect of measurement of blood pressure' Acta Physiol (Oxf). 2018 Apr;222(4):e13010. https://doi.org/10.1111/alpha.13010. Epub 2017 Dec 19. In April 2018, Acta Physiologica published a review entitled: 'Does mean arterial blood pressure scale with body mass in mammals? Effect of measurement of blood pressure'.1 On the basis of data from 114 references including 47 species of mammals, Poulsen et al 20181 investigated whether mean arterial pressure (MAP) scales to body mass (BM) and examined the effect of physiological and methodological confounders such as use of anaesthetics and restraint and the choice of method for determination of blood pressure. We wish to contribute to these findings, by investigating to what extent BM and the vertical distance between the heart and brain contribute to MAP. Physiological variables that encompass a length or a time dimension scale to the size of the animal. A well-known example is the higher heart rate and smaller stroke volume of mice than in, eg an elephant. Also, heart rate decreases during childhood and is likely lower in tall than in small individuals which is also the case for ventilatory frequency.2 In contrast, variables that do not carry a time or a length aspect do not scale to body size. That is the case for, eg concentrations and blood pressure as confirmed for MAP by Poulsen et al1 among animals (weight 0.03-4080 kg; MAP; 61.90-214 mm Hg) not exposed to anaesthesia and ideally free moving. Among animal species, the MAP of the giraffe stands out with a value approximately twice as high as in other animals including humans.1, 3-5 The common consideration is that the high MAP of the giraffe reflects a need to provide the brain an adequate perfusion pressure and that consideration is supported by the position of the carotid baroreceptors. For humans the carotid bifurcation and thereby the position of the baroreceptors vary among individuals establishing a normal distribution along the length of the neck.6 In contrast, for the giraffe and probably for most species the position of the carotid baroreceptors is at the base of the skull.5, 7 Yet, the giraffe is not the only animal that raises its head above the level of the heart. Rather the height of the giraffe represents an extreme among animals for which the brain is lifted above the level of the heart, from the hippo that carries the head slightly above the heart, to animals that carry their heads well above their hearts such as the horse, lama and kangaroo. If the high blood pressure of the giraffe serves to provide its brain with a similar perfusion pressure as established for other animals, then all animals with a long neck would require a larger MAP than animals in which the head is not lifted. Yet, blood pressure for various animals has been related to their weight rather than to the height although they normally carry the head above the heart.1, 7 Thus, in the animals identified by Poulsen et al1 we related the reported MAP to an estimate of the vertical distance from the head to the heart. We measured the distance from the head (ear canal) to the heart (estimated to be situated in the lower thorax, ie 3/4 the distance from the highest level of the thoracic processus spinosus (Th1) to the lowest point of manubrium sterni) in 16 species on display at the Copenhagen Zoo or the Zoological Museum (Table 1). The species all carried their head above the heart and were included in the review by Poulsen et al.1 Table 1. Characteristics of included animals Name Heart to brain distance (cm) Body mass (kg) Mean arterial pressure (mm Hg) Aepyceros melampus 35 30 122 Bos taurus 44 508 130 Camelus bactrianus 54 400 145 Camelus dromedarius 72 369 150 Capra hircus 41 31 95 Ceratotherium simum 61 2495 124 Elephas maximus 56 2960 138 Equus caballus 94 422 127 Giraffa camelopardalis 177 651 214 Lama glama 58 108 132 Macaca fascicularis 11 5 90 Macropus robustus 17 30 93 Ovis aries 27 48 104 Tragulus javanicus 1 1 99 Ursus arctos horribilis 43 59 88 Ursus maritimus 35 145 145 Diplodocus 205 225 Note The grey box indicates missing data. The red box marks that the value is estimated. We found no relation between MAP and the reported BM of the animals (range 1-2960 kg; r = 0.07; P = .31; Figure 1A).1 On the other hand, a relationship was found between the reported MAP of the animals and the estimated distance from the heart to the brain (range 1-177 cm; r = 0.72; P < .01; Figure 1B). The results support that mammals establish a blood pressure that provides sufficient perfusion pressure to the brain, likely through control by the carotid baroreceptors. Interestingly, from the observed correlation in Figure 1B it can be calculated that the dinosaur (diplodocus) at display at the Zoological Museum in Copenhagen, with a 205 cm distance from the heart to the brain, would have had a MAP of 225 mm Hg. The results add to research on the relationship between body height and blood pressure in humans as observed in young healthy men.3, 4 Figure 1Open in figure viewerPowerPoint (A) Mean arterial pressure (mm Hg) over body mass (kg) and (B) Mean arterial pressure (mm Hg) over vertical distance from the heart to the brain (cm), for 16 mammals on display at the Copenhagen Zoo and Zoological Museum. The triangle indicates the estimated mean arterial pressure for diplodocus on display at the Copenhagen Zoological Museum ACKNOWLEDGEMENTS We thank Mads Frost Bertelsen and Daniel Klingberg Johansson for their support and help collecting data. CONFLICTS OF INTEREST The authors have no conflict of interest to declare. REFERENCES 1Poulsen CB, Wang T, Assersen K, Iversen NK, Damkjaer M. Does mean arterial blood pressure scale with body mass in mammals? Effects of measurement of blood pressure. Acta Physiol. 2018; 222(4):e13010. 2Asmussen E, Secher NH, Andersen EA. Heart rate and ventilatory frequency as dimension-dependent variables. Eur J Appl Physiol Occup Physiol. 1981; 46(4): 379- 386. 3Arvedsen SK, Eiken O, Kölegård R, Petersen LG, Norsk P, Damgaard M. Body height and arterial pressure in seated and supine young males during +2 G centrifugation. Am J Physiol Integr Comp Physiol. 2015; 309(9): R1172- R1177. 4Arvedsen SK, Damgaard M, Norsk P. Body height and blood pressure regulation in humans during anti-orthostatic tilting. Am J Physiol Integr Comp Physiol. 2012; 302(8): R984- R989. 5Hargens AR, Millard RW, Pettersson K, Johansen K. Gravitational haemodynamics and oedema prevention in the giraffe. Nature. 1987; 329(6134): 59- 60. 6Querry RG, Smith SA, Strømstad M, Ide K, Secher NH, Raven PB. Anatomical and functional characteristics of carotid sinus stimulation in humans. Am J Physiol Circ Physiol. 2001; 280(5): H2390- H2398. 7White CR, Seymour RS. The role of gravity in the evolution of mammalian blood pressure. Evolution (N Y). 2014; 68(3): 901- 908. Citing Literature Volume228, Issue1January 2020e13407 FiguresReferencesRelatedInformation

In young individuals, oral free fatty acid delays gastric emptying, promotes gut hormone release, and reduces energy intake more than an isocaloric load of triglyceride does. The objective of this study was to compare the effects of the free fatty acid oleic acid (OA) and the triglyceride olive oil (OO) on gastrointestinal motility, gut hormone secretion, and energy intake in older and middle-aged healthy volunteers. In a double-blind, randomized, cross-over, study 10 older (age 83.0 ± 3.4 (mean ± SD) years) and 10 middle-aged (age 43.1 ± 8.9 years) men were examined on two occasions to evaluate the effect of isocaloric and isovolaemic loads of radiolabelled OA or OO on gastric emptying, oro-caecal transit, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretions, and energy intake. Gastric emptying was slower in older than in middle-aged men (lipid p < 0.001, water p = 0.010), while no difference between these groups was found for oro-caecal transit. In comparison with OO, OA caused slower gastric emptying (lipid p < 0.001, water p = 0.020) and faster oro-caecal transit (p = 0.025). Postprandial secretion of GLP-1 and PYY was comparable for older and middle-aged men, as well as for OA and OO. Older men ingested less energy than middle-aged men did (p < 0.001) and their energy intake was lower after OA than OO (p = 0.002). Thus, gastric emptying of an oral lipid load is slower in older than in middle-aged men; gastric emptying is slower and oro-caecal transit faster after OA than OO in both age groups; and older men ingest less energy than middle-aged men and less energy after OA than OO.

Background: Generally, eating salty food items increases thirst. Thirst is also stimulated by the experimental infusion of hypertonic saline. But, in steady state, does the kidney need a higher amount of water to excrete sodium on a high than on a low sodium intake? This issue is still controversial. The purpose of this review is to provide examples of how the kidney handles water in relation to salt intake/output. It is based on re-analysis of previously published studies in which salt intake was adjusted to several different levels in the same subjects, and in databases of epidemiologic studies in populations on an ad libitum diet. Summary and Key Messages: These re-analyses allow us to draw the following conclusions: (1) In a steady state situation, the urine volume (and thus the fluid intake) remains unchanged over a large range of sodium intakes. The adaptation to a higher sodium excretion rests only on changes in urinary sodium concentration. However, above a certain limit, this concentration cannot increase further and the urine volume may then increase. (2) In population studies, it is not legitimate to assume that sodium is responsible for changes in urine volume, since people who eat more sodium also eat more of other nutrients leading to an increase in the excretion of potassium, urea and other solutes, besides sodium. (3) After an abrupt increase in sodium intake, fluid intake is increased in the first few days, but urine volume does not change. The extra fluid drunk is responsible for an increase in body weight.

Recently, it has been proposed, that the blood pressure (BP) lowering effect of gastric bypass surgery not only is explained by the obtained weight loss, but that the anatomical rearrangement of the gut after 'malabsorptive' surgical techniques, such as the laparoscopic Roux-en-Y gastric bypass (LRYGB), may affect BP through a change in a putative 'entero-renal' axis. If so one could anticipate a reduction in BP even before a noticeable weight loss was obtained. The purpose of the present study was to investigate the very early BP response to LRYGB surgery. Ten severely obese hypertensive (mean BMI 40.8 kg/m2) and 10 severely obese normotensive (mean BMI 41.7 kg/m2) patients underwent 24-h ambulatory blood pressure measurements (24 h ABPMs) before LRYGB and again day 1 and day 10 after LRYGB. No change in 24 h BP was observed day 1 after LRYGB. Day 10 after surgery both hypertensive and normotensive patients demonstrated a significant 12.6 mmHg and 9.5 reduction in systolic BP (SBP), respectively. Mean arterial pressure (MAP) decreased by 8.3 and 5.4 mmHg. At day 10 postoperatively, a weight loss of 7.9 kg in the hypertensive patients and 7.0 kg in the normotensive patients was observed. The reduction in BP after LRYGB takes place before any substantial weight loss has occurred. The reason for this remains speculative, but obese hypertensive patients may clearly benefit from the operation even if the goal of achieving 'normoweight' is not obtained.