Background: Changes in renal blood flow (RBF) may play a pathophysiological role in hypertension and kidney disease. However, RBF determination in humans has proven difficult. We aimed to confirm the feasibility of RBF estimation based on positron emission tomography/ computed tomography (PET/CT) and rubidium-82 (82Rb) using the abdominal aorta as input function in a 1-tissue compartment model. Methods: Eighteen healthy subjects underwent two dynamic 82Rb PET/CT scans in two different fields of view (FOV). FOV-A included the left ventricular blood pool (LVBP), the abdominal aorta (AA) and the majority of the kidneys. FOV-B included AA and the kidneys in their entirety. In FOV-A, an input function was derived from LVBP and from AA; in FOV-B from AA. 1-tissue compartmental modeling was performed using tissue time activity curves generated from volumes of interest contouring the kidneys, where the renal clearance of 82Rb is represented by the K1 kinetic parameter. To investigate the correct interpretation of K1, we assumed to first estimate effective renal plasma flow (ERPF) by extrapolating clearance values (ml/min/cm3) to whole kidney values (ml/min) using the estimated total kidney volume. Thereafter, RPF was estimated from ERPF using an assumed extraction fraction (0.89). Lastly, RBF was estimated from RPF using measured haematocrit values. Intra-assay coefficients of variation and inter-observer variation were calculated.Results: For both kidneys, K1 values derived from AA did not differ significantly from values obtained from LVBP, neither were significant differences seen between AA in FOV-A and AA in FOV-B, nor between the right and left kidneys. For both kidneys, the intra-assay coefficients of variation were low (~ 5%) for both input functions. The measured K1 of 2.80 ml/min/cm3 suggests, for young healthy subjects, an estimated total renal perfusion normalized to body surface area of 860 ± 129 ml/min/1.73 m2 and subsequently an estimated RBF of 1494 ± 221 ml/min/1.73 m2. Conclusion: RBF estimation based on PET/CT and 82Rb using AA as input function in a 1-tissue compartment model is feasible in a single FOV. The measured K1 clearance values are most likely representative of ERPF rather than estimated RBF values.

Background Changes in renal perfusion may play a pathophysiological role in hypertension and kidney disease, however to date, no method for renal blood flow (RBF) determination in humans has been implemented in clinical practice. In a previous study, we demonstrated that estimation of renal perfusion based on a single positron emission tomography/computed tomography (PET/CT) scan with Rubidium-82 (82Rb) is feasible and found an approximate 5% intra-assay coefficient of variation for both kidneys, indicative of a precise method.This study’s aim was to determine the day-to day variation of 82Rb PET/CT and to test the method’s ability to detect increased RBF induced by infusion of amino acids. Methods Seventeen healthy subjects underwent three dynamic 82Rb PET/CT scans over two examination days comprising: Day A, a single 8-minute dynamic scan and Day B, two scans performed before (baseline) and after RBF stimulation by a 2-hour amino acid-infusion. The order of examination days was determined by randomization. Time activity curves for arterial and renal activity with a 1-tissue compartment model were used for flow estimation; the K1 kinetic parameter representing renal 82Rb clearance. Day-to-day variation was calculated based on the difference between the unstimulated K1 values on Day A and Day B and paired t-testing was performed to compare K1 values at baseline and after RBF stimulation on Day B. Results Day-to-day variation was observed to be 5.5% for the right kidney and 6.0% for the left kidney (n = 15 quality accepted scans). K1 values determined after amino acid-infusion were significantly higher than pre-infusion values (n = 17, p = 0.001). The mean percentage change in K1 from baseline was 13.2 ± 12.9% (range − 10.4 to 35.5) for the right kidney; 12.9 ± 13.2% (range − 15.7 to 35.3) for the left kidney. Conclusion Day-to-day variation is acceptably low. A significant K1 increase from baseline is detected after application of a known RBF stimulus, indicating that 82Rb PET/CT scanning can provide a precise method for evaluation of RBF and it is able to determine changes herein. Clinical Trial Registration EU Clinical Trials Register, 2017-005008-88. Registered 18/01/2018.

OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.

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PurposeImplementation and comparison of non-invasive dynamic and static whole-body (WB) [18F]NaF PET/CT scan methods to replace invasive bone biopsy, used for quantitative analysis of bone clearance in patients with chronic kidney disease - mineral and bone disorder (CKD-MBD).MethodsSeventeen patients with CKD-MBD underwent a 60-minute dynamic scan followed by a 30-minute static WB scan. Tracer kinetics in four thoracic vertebrae were analyzed using non-linear regression and Patlak analysis using image-derived arterial input functions. We validated the use of a semi-population input function in this population.ResultsSkeletal plasma clearance (Ki) from Patlak analyses correlated well with non-linear regression analysis, but Ki-results using Patlak analysis were lower compared to Ki-results using non-linear regression analysis. However, no significant difference was found between Ki obtained by static WB scans and Ki obtained by dynamic scans using non-linear regression analysis (p=0.29). ConclusionOur results show good correlation between dynamic and static analysis of skeletal plasma clearance with no significant difference between the Ki-results obtained by non-linear regression analysis and the more clinically suitable static scan analysis method. We found lower Ki-results when Patlak analysis was applied. Thus, WB [18F]NaF PET/CT scans can be applied in future studies to measure Ki in CKD-BMD patients, but the results should not be compared uncritically with results obtained by dynamic scans analysis.