The QUEST initiative anemia study in ESRD: rationale and study protocol

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The renal blood flow reserve in healthy humans and patients with atherosclerotic renovascular disease measured by positron emission tomography using [O-15]H2O

Background: Microvascular function plays an important role in ARVD (atherosclerotic renovascular disease). RFR (renal flow reserve), the capacity of renal vasculature to dilate, is known to reflect renal microvascular function. In this pilot study, we assessed PET (positron emission tomography)-based RFR values of healthy persons and renal artery stenosis patients.Seventeen patients with ARVD and eight healthy subjects were included in the study. Intravenous enalapril 1 mg was used as a vasodilatant, and the maximum response (blood pressure and RFR) to it was measured at 40 min. Renal perfusion was measured by means of oxygen-15-labeled water PET. RFR was calculated as a difference of stress flow and basal flow and was expressed as percent [(stress blood flow - basal blood flow)/basal blood flow] x 100%.Results: RFR of the healthy was 22%. RFR of the stenosed kidneys of bilateral stenosis patients (27%) was higher than that of the stenosed kidneys of unilateral stenosis patients (15%). RFR of the contralateral kidneys of unilateral stenosis patients was 21%. There was no difference of statistical significance between RFR values of ARVD subgroups or between ARVD subgroups and the healthy. In the stenosed kidneys of unilateral ARVD patients, stenosis grade of the renal artery correlated negatively with basal (p = 0.04) and stress flow (p = 0.02). Dispersion of RFR values was high.Conclusions: This study is the first to report [O-15]H2O PET-based RFR values of healthy subjects and ARVD patients in humans. The difference between RFR values of ARVD patients and the healthy did not reach statistical significance perhaps because of high dispersion of RFR values. [O-15]H2O PET is a valuable non-invasive and quantitative method to evaluate renal blood flow though high dispersion makes imaging challenging. Larger studies are needed to get more information about [O-15]H2O PET method in evaluation of renal blood flow

Association of maximal stress ergometry performance with troponin T and abdominal aortic calcification score in advanced chronic kidney disease

Background: Cardiac biomarkers Troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (proBNP) and abdominal aortic calcification score (AAC) are associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). The effects of cardiac biomarkers and AAC on maximal exercise capacity in CKD are unknown and were studied.Methods: One hundred seventy-four CKD 4-5 patients not on maintenance dialysis underwent maximal bicycle ergometry stress testing, lateral lumbar radiograph to study AAC, echocardiography and biochemical assessments.Results: The subjects with proportional maximal ergometry workload (WMAX%) less than 50% of the expected values had higher TnT, proBNP, AAC, left ventricular end-diastolic diameter, left ventricular mass index, E/e' and pulse pressure, and lower global longitudinal strain compared to the better performing patients. TnT (beta = - 0.09, p = 0.02), AAC (beta = - 1.67, p Conclusions: TnT and AAC are independently associated with maximal ergometry stress test workload in patients with advanced CKD.</p

Prognostic imaging biomarkers for diabetic kidney disease (iBEAt): Study protocol

Background: Diabetic kidney disease (DKD) remains one of the leading causes of premature death in diabetes. DKD is classified on albuminuria and reduced kidney function (estimated glomerular filtration rate (eGFR)) but these have modest value for predicting future renal status. There is an unmet need for biomarkers that can be used in clinical settings which also improve prediction of renal decline on top of routinely available data, particularly in the early stages. The iBEAt study of the BEAt-DKD project aims to determine whether renal imaging biomarkers (magnetic resonance imaging (MRI) and ultrasound (US)) provide insight into the pathogenesis and heterogeneity of DKD (primary aim) and whether they have potential as prognostic biomarkers in DKD (secondary aim). Methods: iBEAt is a prospective multi-centre observational cohort study recruiting 500 patients with type 2 diabetes (T2D) and eGFR ≥30 ml/min/1.73m2. At baseline, blood and urine will be collected, clinical examinations will be performed, and medical history will be obtained. These assessments will be repeated annually for 3 years. At baseline each participant will also undergo quantitative renal MRI and US with central processing of MRI images. Biological samples will be stored in a central laboratory for biomarker and validation studies, and data in a central data depository. Data analysis will explore the potential associations between imaging biomarkers and renal function, and whether the imaging biomarkers improve the prediction of DKD progression. Ancillary substudies will: (1) validate imaging biomarkers against renal histopathology; (2) validate MRI based renal blood flow measurements against H2O15 positron-emission tomography (PET); (3) validate methods for (semi-)automated processing of renal MRI; (4) examine longitudinal changes in imaging biomarkers; (5) examine whether glycocalyx and microvascular measures are associated with imaging biomarkers and eGFR decline; (6) explore whether the findings in T2D can be extrapolated to type 1 diabetes. Discussion: iBEAt is the largest DKD imaging study to date and will provide valuable insights into the progression and heterogeneity of DKD. The results may contribute to a more personalised approach to DKD management in patients with T2D. Trial registration: Clinicaltrials.gov (NCT03716401)

Prognostic imaging biomarkers for diabetic kidney disease (iBEAt):study protocol

Background: Diabetic kidney disease (DKD) remains one of the leading causes of premature death in diabetes. DKD is classified on albuminuria and reduced kidney function (estimated glomerular filtration rate (eGFR)) but these have modest value for predicting future renal status. There is an unmet need for biomarkers that can be used in clinical settings which also improve prediction of renal decline on top of routinely available data, particularly in the early stages. The iBEAt study of the BEAt-DKD project aims to determine whether renal imaging biomarkers (magnetic resonance imaging (MRI) and ultrasound (US)) provide insight into the pathogenesis and heterogeneity of DKD (primary aim) and whether they have potential as prognostic biomarkers in DKD (secondary aim). Methods: iBEAt is a prospective multi-centre observational cohort study recruiting 500 patients with type 2 diabetes (T2D) and eGFR ≥30 ml/min/1.73m2. At baseline, blood and urine will be collected, clinical examinations will be performed, and medical history will be obtained. These assessments will be repeated annually for 3 years. At baseline each participant will also undergo quantitative renal MRI and US with central processing of MRI images. Biological samples will be stored in a central laboratory for biomarker and validation studies, and data in a central data depository. Data analysis will explore the potential associations between imaging biomarkers and renal function, and whether the imaging biomarkers improve the prediction of DKD progression. Ancillary substudies will: (1) validate imaging biomarkers against renal histopathology; (2) validate MRI based renal blood flow measurements against H2O15 positron-emission tomography (PET); (3) validate methods for (semi-)automated processing of renal MRI; (4) examine longitudinal changes in imaging biomarkers; (5) examine whether glycocalyx and microvascular measures are associated with imaging biomarkers and eGFR decline; (6) explore whether the findings in T2D can be extrapolated to type 1 diabetes. Discussion: iBEAt is the largest DKD imaging study to date and will provide valuable insights into the progression and heterogeneity of DKD. The results may contribute to a more personalised approach to DKD management in patients with T2D. Trial registration: Clinicaltrials.gov (NCT03716401)

Elevation of the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline: a blood pressure-independent beneficial effect of angiotensin I-converting enzyme inhibitors

Blockade of the renin-angiotensin system (RAS) is well recognized as an essential therapy in hypertensive, heart, and kidney diseases. There are several classes of drugs that block the RAS; these drugs are known to exhibit antifibrotic action. An analysis of the molecular mechanisms of action for these drugs can reveal potential differences in their antifibrotic roles. In this review, we discuss the antifibrotic action of RAS blockade with an emphasis on the potential importance of angiotensin I-converting enzyme (ACE) inhibition associated with the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP)

Prognostic imaging biomarkers for diabetic kidney disease (iBEAt): study protocol

Background: Diabetic kidney disease (DKD) remains one of the leading causes of premature death in diabetes. DKD is classified on albuminuria and reduced kidney function (estimated glomerular filtration rate (eGFR)) but these have modest value for predicting future renal status. There is an unmet need for biomarkers that can be used in clinical settings which also improve prediction of renal decline on top of routinely available data, particularly in the early stages. The iBEAt study of the BEAt-DKD project aims to determine whether renal imaging biomarkers (magnetic resonance imaging (MRI) and ultrasound (US)) provide insight into the pathogenesis and heterogeneity of DKD (primary aim) and whether they have potential as prognostic biomarkers in DKD (secondary aim). Methods: iBEAt is a prospective multi-centre observational cohort study recruiting 500 patients with type 2 diabetes (T2D) and eGFR >= 30 ml/min/1.73m(2). At baseline, blood and urine will be collected, clinical examinations will be performed, and medical history will be obtained. These assessments will be repeated annually for 3 years. At baseline each participant will also undergo quantitative renal MRI and US with central processing of MRI images. Biological samples will be stored in a central laboratory for biomarker and validation studies, and data in a central data depository. Data analysis will explore the potential associations between imaging biomarkers and renal function, and whether the imaging biomarkers improve the prediction of DKD progression. Ancillary substudies will: (1) validate imaging biomarkers against renal histopathology; (2) validate MRI based renal blood flow measurements against H2O15 positron-emission tomography (PET); (3) validate methods for (semi-)automated processing of renal MRI; (4) examine longitudinal changes in imaging biomarkers; (5) examine whether glycocalyx and microvascular measures are associated with imaging biomarkers and eGFR decline; (6) explore whether the findings in T2D can be extrapolated to type 1 diabetes. Discussion: iBEAt is the largest DKD imaging study to date and will provide valuable insights into the progression and heterogeneity of DKD. The results may contribute to a more personalised approach to DKD management in patients with T2D.</div