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Abstract Background Patients with chronic kidney disease (CKD) are susceptible to vascular calcification and vitamin K deficiency. Matrix gla protein (MGP) is a potent inhibitor of calcification requiring vitamin K for activation. Inactive MGP, i.e. dephosphorylated uncarboxylated MGP (dp-ucMGP), is frequently elevated in CKD along with protein induced by vitamin K absence (PIVKA-II). We investigated whether dp-ucMGP and PIVKA-II are useful markers of aortic calcification in CKD. Methods Patients with normal or reduced kidney function underwent a non-contrast computed tomography scan of the entire aorta with subsequent blinded standard calcification scoring of the aortic wall ad modum Agatston. Blood samples were analyzed for plasma concentrations of dp-ucMGP and PIVKA-II. Results 141 patients (104 with CKD stage 3–5) were included. In patients with/without CKD median (interquartile range) were dp-ucMGP 543 (503–744)/1078 (835–1682) pmol/l (P

Abstract Fibromuscular dysplasia (FMD) is a disease of the musculature of arterial walls leading to stenoses, aneurysms, and dissections. The purpose of this report was to summarize the evidence for (1) one‐time routine imaging from brain‐to‐pelvis and (2) lifelong antiplatelet therapy, for example, aspirin, for patients diagnosed with FMD as suggested by an international consensus report from 2019. PubMed was systematically searched, and the evidence providing a basis for the current consensus points, as well as articles published since, were reviewed. In four registries evaluating patients with FMD, the prevalence of multivessel involvement, aneurysms, and dissections was reported to be 43.5%–66.3%, 21.6%–30.6%, and 5.6%–28.1%, respectively. Any antiplatelet drug was used in 72.9% of patients, and aspirin was prescribed in up to 70.2% of patients. Based on the high prevalence of vascular manifestations, their associated morbidity, and the potential for endovascular or surgical intervention, the suggestion of one‐time brain‐to‐pelvis screening with computed tomography angiography or magnetic resonance angiography is well supported. Contrarily, the evidence to support the consensus statement of lifelong antiplatelet therapy to all patients in the absence of contraindications is more uncertain since a beneficial effect has not been demonstrated specifically in patients with fibromuscular dysplasia. Therefore, until the efficacy and safety of primary thromboprophylaxis have been demonstrated in this patient group specifically, it may be equally appropriate to only use antiplatelet agents in patients with a clear indication after individual evaluation according to risk factors for thrombotic and thromboembolic complications.

BackgroundSodium-glucose-cotransporter 2 inhibitors (SGLT2is) have revolutionized the treatment of type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD), reducing the risk of cardiovascular and renal end points by up to 40%. The underlying mechanisms are not fully understood. ObjectiveThe study aims to examine the effects of empagliflozin versus placebo on renal hemodynamics, sodium balance, vascular function, and markers of the innate immune system in patients with DM2, DM2 and CKD, and nondiabetic CKD. MethodsWe conducted 3 double-blind, crossover, randomized controlled trials, each with identical study protocols but different study populations. We included patients with DM2 and preserved kidney function (estimated glomerular filtration rate >60 mL/min/1.73 m2), DM2 and CKD, and nondiabetic CKD (both with estimated glomerular filtration rate 20-60 mL/min/1.73 m2). Each participant was randomly assigned to 4 weeks of treatment with either 10 mg of empagliflozin once daily or a matching placebo. After a wash-out period of at least 2 weeks, participants were crossed over to the opposite treatment. End points were measured at the end of each treatment period. The primary end point was renal blood flow measured with 82Rubidium positron emission tomography–computed tomography (82Rb-PET/CT). Secondary end points include glomerular filtration rate measured with 99mTechnetium-diethylene-triamine-pentaacetate (99mTc-DTPA) clearance, vascular function assessed by forearm venous occlusion strain gauge plethysmography, measurements of the nitric oxide (NO) system, water and sodium excretion, body composition measurements, and markers of the complement immune system. ResultsRecruitment began in April 2021 and was completed in September 2022. Examinations were completed by December 2022. In total, 49 participants completed the project: 16 participants in the DM2 and preserved kidney function study, 17 participants in the DM2 and CKD study, and 16 participants in the nondiabetic CKD study. Data analysis is ongoing. Results are yet to be published. ConclusionsThis paper describes the rationale, design, and methods used in a project consisting of 3 double-blind, crossover, randomized controlled trials examining the effects of empagliflozin versus placebo in patients with DM2 with and without CKD and patients with nondiabetic CKD, respectively. Trial RegistrationEU Clinical Trials Register 2019-004303-12; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004303-12, EU Clinical Trials Register 2019-004447-80; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004447-80, EU Clinical Trials Register 2019-004467-50; https://www.clinicaltrialsregister.eu/ctr-search/search?query=and+2019-004467-50 International Registered Report Identifier (IRRID)DERR1-10.2196/56067

The aim was to establish combined H215O PET/MRI during ex vivo normothermic machine perfusion (NMP) of isolated porcine kidneys. We examined whether changes in renal arterial blood flow (RABF) are accompanied by changes of a similar magnitude in renal blood perfusion (RBP) as well as the relation between RBP and renal parenchymal oxygenation (RPO). Methods: Pig kidneys (n = 7) were connected to a NMP circuit. PET/MRI was performed at two different pump flow levels: a blood-oxygenation-level-dependent (BOLD) MRI sequence performed simultaneously with a H215O PET sequence for determination of RBP. Results: RBP was measured using H215O PET in all kidneys (flow 1: 0.42–0.76 mL/min/g, flow 2: 0.7–1.6 mL/min/g). We found a linear correlation between changes in delivered blood flow from the perfusion pump and changes in the measured RBP using PET imaging (r2 = 0.87). Conclusion: Our study demonstrated the feasibility of combined H215O PET/MRI during NMP of isolated porcine kidneys with tissue oxygenation being stable over time. The introduction of H215O PET/MRI in nephrological research could be highly relevant for future pre-transplant kidney evaluation and as a tool for studying renal physiology in healthy and diseased kidneys.

Purpose Hypertension is common in kidney transplant recipients (KTRs). For the evaluation of blood pressure (BP), 24-h ambulatory BP measurements (ABPM) are considered superior to usual office measurements but are also resource demanding and troublesome to many patients. We therefore evaluated the use of unattended automated office BP (AOBP) during the first year following living donor kidney transplantation and compared AOBP with ABPM as obtained 12 months after transplantation. Materials and methods Data were retrieved from a cohort of 57 KTRs (mean age 45 ± 14 years, 75% males) who all received kidneys from living donors and had a good graft function (estimated glomerular filtration rate (eGFR) 52 ± 16 ml/min/1.73 m2 at 12 months). Unattended AOBP was measured at each visit to the outpatient clinic using the BpTru® device, while ABPM was obtained by Spacelabs® equipment before and 12 months after transplantation. Results AOBP remained stable from month 2 (130.2 ± 10.8/82.2 ± 7.8 mmHg) to month 12 (129.0 ± 12.8/83.1 ± 9.6 mmHg) post-transplantation. At 12 months follow-up, ambulatory daytime systolic BP was slightly higher than AOBP (132.7 ± 10.7 vs. 129.4 ± 12.2 mmHg, p = 0.04), while diastolic BP was similar (82.7 ± 7.7 vs. 82.0 ± 10.2 mmHg). Using Bland–Altman plots, 95% limits of agreements were −17.9 to 24.5 mmHg for systolic and −16.5 to 15.1 mmHg for diastolic BP. When considering a target BP of ≤130/

Abstract Background Patients with kidney failure treated with dialysis or kidney transplantation experience difficulties maintaining employment due to the condition itself and the treatment. We aimed to establish the rate of employment before and after initiation of dialysis and kidney transplantation and to identify predictors of employment during dialysis and posttransplant. Methods This systematic review and meta-analysis were carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for studies that included employment rate in adults receiving dialysis or a kidney transplant. The literature search included cross-sectional or cohort studies published in English between January 1966 and August 2020 in the PubMed, Embase, and Cochrane Library databases. Data on employment rate, study population, age, gender, educational level, dialysis duration, kidney donor, ethnicity, dialysis modality, waiting time for transplantation, diabetes, and depression were extracted. Quality assessment was performed using the Newcastle–Ottawa Scale. Meta-analysis for predictors for employment, with odds ratios and confidence intervals, and tests for heterogeneity, using chi-square and I2 statistics, were calculated. PROSPERO registration number: CRD42020188853. Results Thirty-three studies included 162,059 participants receiving dialysis, and 31 studies included 137,742 participants who received kidney transplantation. Dialysis patients were on average 52.6 years old (range: 16–79; 60.3% male), and kidney transplant patients were 46.7 years old (range: 18–78; 59.8% male). The employment rate (weighted mean) for dialysis patients was 26.3% (range: 10.5–59.7%); the employment rate was 36.9% pretransplant (range: 25–86%) and 38.2% posttransplant (range: 14.2–85%). Predictors for employment during dialysis and posttransplant were male, gender, age, being without diabetes, peritoneal dialysis, and higher educational level, and predictors of posttransplant: pretransplant employment included transplantation with a living donor kidney, and being without depression. Conclusions Patients with kidney failure had a low employment rate during dialysis and pre- and posttransplant. Kidney failure patients should be supported through a combination of clinical and social measures to ensure that they remain working.

Introduction: Chronic kidney disease (CKD) is associated with cardiovascular disease (CVD) and death. Albuminuria is an established risk factor, but additional biomarkers predicting CKD progression or CVD are needed. Arterial stiffness is an easily measurable parameter that has been associated with CVD and mortality. We evaluated the ability of carotid-femoral pulse wave velocity (PWV) and urine albumin-creatinine (UAC) ratio to predict CKD progression, cardiovascular events and mortality in a cohort of CKD patients. Methods: In CKD stage 3-5 patients PWV and UAC were measured at baseline. CKD progression was defined as 50% decline in estimated glomerular filtration rate (eGFR), initiation of dialysis or renal transplantation. A composite endpoint was defined as CKD progression, myocardial infarction, stroke, or death. Endpoints were analyzed using Cox regression analysis adjusted for possible confounders. Results: We included 181 patients (median age 69 [interquartile range 60-75] years, 67% males) with a mean eGFR of 37±12 ml/min/1.73 m2 and UAC 52 [5-472] mg/g. Mean PWV was 10.6 m/s. Median follow-up until first event was 4 [3-6] years with 44 and 89 patients reaching a CKD progression or composite endpoint, respectively. UAC (g/g) significantly predicted both CKD progression (HR 1.5 [1.2;1.8]) and composite endpoints (HR 1.4 [1.1;1.7]) in adjusted Cox regression. In contrast, PWV (m/s) was not associated with neither CKD progression (HR 0.99 [0.84;1.18]) nor the composite endpoint (HR 1.03 [0.92;1.15]). Conclusion: In an ageing CKD population, UAC predicted both CKD progression and a composite endpoint of CKD progression, cardiovascular events, or death, while PWV did not.

Background Estimated pulse wave velocity (ePWV) calculated by equations using age and blood pressure has been suggested as a new marker of mortality and cardiovascular risk. However, the prognostic potential of ePWV during long‐term follow‐up in patients with symptoms of stable angina remains unknown. Methods and Results In this study, ePWV was calculated in 25 066 patients without diabetes, previous myocardial infarction (MI), stroke, heart failure, or valvular disease (mean age 63.7±10.5 years, 58% male) with stable angina pectoris undergoing elective coronary angiography during 2003 to 2016. Multivariable Cox models were used to assess the association with incident all‐cause mortality, MI, and stroke. Discrimination was assessed using Harrell´s C‐index. During a median follow‐up period of 8.5 years (interquartile range 5.5–11.3 years), 779 strokes, 1233 MIs, and 4112 deaths were recorded. ePWV was associated with all‐cause mortality (hazard ratio [HR] per 1 m/s, 1.13; 95% CI, 1.05–1.21) and MI (HR per 1 m/s 1.23, 95% CI, 1.09–1.39) after adjusting for age, systolic blood pressure, body mass index, smoking, estimated glomerular filtration rate, Charlson Comorbidity Index score, antihypertensive treatment, statins, aspirin, and number of diseased coronary arteries. Compared with traditional risk factors, the adjusted model with ePWV was associated with a minor but likely not clinically relevant increase in discrimination for mortality, 76.63% with ePWV versus 76.56% without ePWV, P

Abstract Repeated cuff‐based blood pressure (BP) measurements may cause discomfort resulting in stress and erroneous recording values. SOMNOtouch NIBP is an alternative cuff‐less BP measurement device that calculates changes in BP based on changes in pulse transit time (PTT) and a software algorithm. The device is calibrated with a single upper arm cuff‐based BP measurement. We tested the device against a validated 24‐h ambulatory BP monitoring (ABPM) device using both the previous (SomBP1) and the current software algorithm (SomBP2). In this study, 51 patients (mean age ± SD 61.5 ± 13.0 years) with essential hypertension underwent simultaneous 24‐h ABPM with the SOMNOtouch NIBP on the left arm and a standard cuff‐based oscillometric device on the right arm (OscBP). We found that mean daytime systolic BP (SBP) with OscBP was 140.8 ± 19.7 compared to 148.0 ± 25.2 (P = .008) and 146.9 ± 26.0 mmHg (P = .034) for SomBP1 and SomBP2, respectively. Nighttime SBP with OscBP was 129.5 ± 21.1 compared with 146.1 ± 25.8 (P

Background The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high‐risk clinical presentations as defined in a national protocol developed in 2015. Methods and Results Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high‐risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24‐hour ambulatory systolic blood pressure was 166.2 mm Hg (95% CI, 162.0–170.4), the defined daily dose of antihypertensive medication was 6.5 (95% CI, 5.8–7.3), and the estimated glomerular filtration rate was 41.1 mL/min per 1.73m2 (95% CI, 36.6–45.6). In 96 patients with available 3‐month follow‐up data, mean 24‐hour ambulatory systolic blood pressure decreased by 19.6 mm Hg (95% CI, 15.4–23.8; P

Background: Mycophenolic acid (MPA) is a potent immunosuppressive agent used in solid organ transplantation. MPA exhibits large interindividual variation in dose-normalized plasma concentrations but is nevertheless usually prescribed as a fixed dose without use of therapeutic drug monitoring (TDM). Data on the effect of corticosteroid (CS) treatment on MPA concentrations during concomitant tacrolimus treatment remains sparse.Methods: Data is based on TDM of MPA area under the concentration curve (AUC) in 210 renal transplant recipients participating in the prospective, randomized, controlled, multi-center trial (SAILOR) where a steroid-free immunosuppressive regimen with mycophenolate mofetil (MMF) and low-dose tacrolimus was compared with a conventional prednisolone-based treatment regimen. Multilevel mixed-effects linear regression post-hoc analyses of MPA AUC was performed.Results: Median MPA AUC at baseline (within the first 2 weeks post-transplant) in patients taking 2 g MMF daily was 53 mg*h/L (interquartile range: 43–69 mg*h/L, min: 24—max: 117 mg*h/L). Between-patient variation in MPA AUC was up to 5-fold on the same MMF dose. Patients in the steroid-free group had 12.5% lower (95% CI; 3.2–20.9%, p = 0.01) MPA AUC levels at baseline compared to the steroid treated group. During follow-up (14 days–2 years post-transplant) there were no significant differences in MPA AUC between the groups with MPA AUC being 4.2% lower (95% CI: −4.8%−12,5%, p = 0.35) in the steroid-free vs standard treatment group in restricted analysis after multivariate adjustment for tacrolimus trough level, body weight, time after transplantation and MMF dose. MMF dose was positively correlated with MPA AUC (p < 0.001) whereas body weight was negatively correlated with MPA AUC (p < 0.001). MPA AUC was 0.4% (95% CI: 0.2–0.6%, p < 0.001) lower per 1 kg increase in weight. Tacrolimus trough levels had no significant effect on MPA AUC.Conclusion: Immunosuppression with CS during concomitant tacrolimus treatment was shortly after transplantation associated with a significantly higher MPA exposure but the effect was small and not maintained during follow-up. Low body weight was associated with higher MPA exposure, which suggests a potential for weight adjusted MMF dosing.

Background: Central blood pressure (BP) assessed noninvasively considerably underestimates true invasively measured aortic BP in chronic kidney disease (CKD) patients. The difference between the estimated and the true aortic BP increases with decreasing estimated glomerular filtration rates (eGFR). The present study investigated whether aortic calcification affects noninvasive estimates of central BP. Methods: Twenty-four patients with CKD stage 4–5 undergoing coronary angiography and an aortic computed tomography scan were included (63% males, age [mean ± SD ] 53 ± 11 years, and eGFR 9 ± 5 mL/min/1.73 m2). Invasive aortic BP was measured through the angiography catheter, while non-invasive central BP was obtained using radial artery tonometry with a SphygmoCor® device. The Agatston calcium score (CS) in the aorta was quantified on CT scans using the CS on CT scans. Results: The invasive aortic systolic BP (SBP) was 152 ± 23 mm Hg, while the estimated central SBP was 133 ± 20 mm Hg. Ten patients had a CS of 0 in the aorta, while 14 patients had a CS >0 in the aorta. The estimated central SBP was lower than the invasive aortic SBP in patients with aortic calcification compared to patients without (mean difference 8 mm Hg, 95% CI 0.3–16; p = 0.04). The brachial SBP was lower than the aortic SBP in patients with aortic calcification compared to patients without (mean difference 10 mm Hg, 95% CI 2–19; p = 0.02). Conclusion: In patients with advanced CKD the presence of aortic calcification is associated with a higher difference between invasively measured central aortic BP and non-invasive estimates of central BP as compared to patients without calcifications.

Objectives: To investigate, whether renal denervation (RDN) improves arterial stiffness, central blood pressure (C-BP) and heart rate variability (HRV) in patients with treatment resistant hypertension. Methods: ReSET was a randomized, sham-controlled, double-blinded trial (NCT01459900). RDN was performed by a single experienced operator using the Medtronic unipolar Symplicity FlexTM catheter. C-BP, carotid-femoral pulse wave velocity (PWV), and HRV were obtained at baseline and after six months with the SphygmoCor®-device. Results: Fifty-three patients (77% of the ReSET-cohort) were included in this substudy. The groups were similar at baseline (SHAM/RDN): n = 27/n = 26; 78/65% males; age 59 ± 9/54 ± 8 years (mean ± SD); systolic brachial BP 158 ± 18/154 ± 17 mmHg; systolic 24-hour ambulatory BP 153 ± 14/151 ± 13 mmHg. Changes in PWV (0.1 ± 1.9 (SHAM) vs. −0.6 ± 1.3 (RDN) m/s), systolic C-BP (−2 ± 17 (SHAM) vs. −8 ± 16 (RDN) mmHg), diastolic C-BP (−2 ± 9 (SHAM) vs. −5 ± 9 (RDN) mmHg), and augmentation index (0.7 ± 7.0 (SHAM) vs. 1.0 ± 7.4 (RDN) %) were not significantly different after six months. Changes in HRV-parameters were also not significantly different. Baseline HRV or PWV did not predict BP-response after RDN. Conclusions: In a sham-controlled setting, there were no significant effects of RDN on arterial stiffness, C-BP and HRV. Thus, the idea of BP-independent effects of RDN on large arteries and cardiac autonomic activity is not supported.

Aim: Established essential hypertension (EH) is associated with increased arterial stiffness and peripheral resistance, but the extent of vascular changes in persons genetically predisposed for EH is uncertain. Methods: Participants from the Danish Hypertension Prevention Project (DHyPP) (having two hypertensive parents) (n = 95, 41±1 years, 53% males) were compared to available spouses (n = 45, age 41±1 years, 43% males). The subjects had measurements of ambulatory blood pressure (BP), left ventricular mass (LVM), pulse wave velocity (PWV), central BP and augmentation index (AIx) in addition to forearm resting and minimal resistance (Rrest and Rmin). Results: DHyPP subjects with and without spouses were comparable and the DHyPP cohort, as compared to spouses, had higher 24-hour mean BP (94±1 vs. 88±1 mmHg, P < 0.01), LVM (90±2 vs. 80±2 g/m2, P < 0.01), central systolic BP (119±2 vs. 111±2 mmHg, P < 0.01) and AIx (15.1±1.2 vs. 10.5±1.7%, P < 0.01), but similar values of carotid-femoral PWV (7.3±0.1 vs. 7.1±0.2 m/s), Rrest (51±2 vs. 51±3 mmHg/ml/min/100 ml) and log Rmin (0.57±0.02 vs. 0.55±0.02 mmHg/ml/min/100 ml). AIx, Rrest and Rmin were higher in female as compared to male DHyPP participants (P < 0.01 for all) and the same was true for AIx and Rmin among spouses (P < 0.05). Using multiple linear regression analysis adjusting for gender, age, body mass index, 24-hour BP, 24-hour sodium excretion and creatinine clearance, AIx remained elevated in DHyPP subjects (3.4% [0.18; 6.60], P = 0.039). Furthermore, AIx was linearly associated with Rrest and Rmin. Conclusion: Young to middle-aged individuals genetically predisposed for EH display increased AIx, while vascular stiffness and peripheral resistance are still normal.