INTRODUCTION:A decrease in renal perfusion during acute kidney injury (AKI) due to critical COVID-19 has previously been demonstrated. The objective of this study was to compare the effects of plasma expansion with a standardized fluid bolus on renal perfusion in critically ill patients with AKI compared to similar patients without AKI. METHODS:A case control study design was used to investigate group differences before and after a standardized intervention. ICU-treated COVID-19 patients without underlying kidney disease were assigned to two groups based on KDIGO Creatinine criteria for AKI. Renal perfusion was assessed by magnetic resonance imaging using phase contrast and arterial spin labeling before and directly after plasma expansion with 7.5 mL/kg Ringer's Acetate (Baxter). Arithmetic means of mean arterial pressures (MAP) recorded before and after plasma infusion were compared. Data was analyzed with a mixed model repeated measures ANOVA for all kidneys using a random effect to account for research subjects. RESULTS:Nine patients with AKI and eight without were included in the study. The hemodynamic response to plasma expansion was similar in both groups, with increases in MAP by 9 mmHg (95% CI 0.5-18) and 15 mmHg (95% CI 5-24) in patients with and without AKI, respectively. Total renal perfusion and cortical perfusion were not significantly changed by plasma expansion in either group. There was a reduction of medullary perfusion in patients without AKI from 55 (95% CI 39-79) to 34 (95% CI 24-48) mL/min/100 g (p = .0027). CONCLUSION:Plasma expansion with a standardized fluid bolus did not increase renal perfusion in critically ill patients with COVID-19, with or without AKI.

Study objective: To investigate if there are any differences in total renal blood flow, regional renal perfusion, renal oxygenation or renal tissue properties, studied by non-invasive MRI, in patients having recovered from severe COVID-19 with different grades of acute kidney injury (AKI). Hypothesis: We hypothesize that the decrease in renal blood flow and perfusion that our research group have previously found in severe COVID-19 patients with AKI 1 may persist together with possible renal edema and development of fibrosis. Material and methods: We identified patients with AKI grade 3 from a cohort of patients previously treated in the intensive care unit for severe COVID-19 with respiratory failure. These patients were matched to possible extent regarding age, sex, height, weight, body mass index (BMI) and body surface area (BSA) with patients from the same cohort that had AKI grade 1 and patients that did not have AKI. A total of 22 patients were included. Because of common occurrence of oliguria without a reduction of glomerular filtration, AKI grade was determined using the Kidney Disease Improving Global Outcome (KDIGO) creatinine criteria only. All patients had a record of a plasma creatinine inside normal range within two years prior to ICU care, and had no history of renal disease. Comorbidities were common in the study population. Follow up examination was performed approximately five months after the patients were admitted the ICU. Results: Significant differences in cortical and medullary ADC were demonstrated between the study groups. Both cortical and medullary ADC was significantly reduced in the ‘AKI grade 3’ group compared to the ‘no AKI’ group and the ‘AKI grade 1’ group. Total renal blood flow was significantly lower in the ‘AKI grade 3’ group compared to the ‘no AKI’ group and global renal perfusion was significantly lower in the ‘AKI grade 3’ group compared to the ‘no AKI’ and ‘AKI grade 1’ groups. No significant differences in either cortical or medullary perfusion were seen between the groups. Cortical and medullary oxygenation and renal vein oxygen saturation did not differ significantly between the groups. Conclusion: In this study we demonstrates that, approximately five months after intensive care for severe COVID-19, patients that had high grades of AKI during hospitalization have reduced cortical and medullary ADC together with reduced total renal blood flow and global renal perfusion compared to similar patients that did not have AKI. These findings might indicate development of renal fibrosis. No differences regarding renal oxygenation were observed between the studied groups. 1. Luther T, Eckerbom P, Cox E, Lipcsey M, Bulow S, Hultstrom M, et al. Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging: a prospective case control study. Crit Care. 2022;26(1):262. Public and private funding sources. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract Background Renal hypoperfusion has been suggested to contribute to the development of acute kidney injury (AKI) in critical COVID-19. However, limited data exist to support this. We aim to investigate the differences in renal perfusion, oxygenation and water diffusion using multiparametric magnetic resonance imaging in critically ill COVID-19 patients with and without AKI. Methods A prospective case–control study where patients without prior kidney disease treated in intensive care for respiratory failure due to COVID-19 were examined. Kidney Disease: Improving Global Outcomes Creatinine criteria were used for group allocation. Main comparisons were tested using Mann–Whitney U test. Results Nineteen patients were examined, ten with AKI and nine without AKI. Patients with AKI were examined in median 1 [0–2] day after criteria fulfillment. Age and baseline Plasma-Creatinine were similar in both groups. Total renal blood flow was lower in patients with AKI compared with patients without (median 645 quartile range [423–753] vs. 859 [746–920] ml/min, p = 0.037). Regional perfusion was reduced in both cortex (76 [51–112] vs. 146 [123–169] ml/100 g/min, p = 0.015) and medulla (28 [18–47] vs. 47 [38–73] ml/100 g/min, p = 0.03). Renal venous saturation was similar in both groups (72% [64–75] vs. 72% [63–84], ns.), as was regional oxygenation (R 2*) in cortex (17 [16–19] vs. 17 [16–18] 1/s, ns.) and medulla (29 [24–39] vs. 27 [23–29] 1/s, ns.). Conclusions In critically ill COVID-19 patients with AKI, the total, cortical and medullary renal blood flows were reduced compared with similar patients without AKI, whereas no differences in renal oxygenation were demonstrable in this setting. Trial registration ClinicalTrials ID: NCT02765191 , registered May 6 2014 and updated May 7 2020. Graphic Abstract

BackgroundPhase‐contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC‐MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC‐MRI as a clinically useful tool.PurposeTo build technical recommendations for the acquisition, processing, and analysis of renal 2D PC‐MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies.Study TypeSystematic consensus process using a modified Delphi method.PopulationNot applicable.Sequence Field/StrengthRenal fast gradient echo‐based 2D PC‐MRI.AssessmentAn international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4–10) years of experience in 2D PC‐MRI formulated consensus statements on renal 2D PC‐MRI in two rounds of surveys. Starting from a recently published systematic review article, literature‐based and data‐driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated.Statistical TestsConsensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60–74% agreement among the experts.ResultsAmong 60 statements, 57 (95%) achieved consensus after the second‐round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC‐MRI data acquisition, processing, and reporting.Data ConclusionThese recommendations might promote a widespread adoption of renal PC‐MRI, and may help foster the set‐up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC‐MRI.Level of Evidence1Technical Efficacy Stage1

Circadian regulation of kidney function is involved in maintaining whole body homeostasis, and dysfunctional circadian rhythm can potentially be involved in disease development. Magnetic resonance imaging (MRI) provides reliable and reproducible repetitive estimates of kidney function noninvasively without the risk of adverse events associated with contrast agents and ionizing radiation. The purpose of this study was to estimate circadian variations in kidney function in healthy human subjects with MRI and to relate the findings to urinary excretions of electrolytes and markers of kidney function. Phase-contrast imaging, arterial spin labeling, and blood oxygen level-dependent transverse relaxation rate (R 2 *) mapping were used to assess total renal blood flow and regional perfusion as well as intrarenal oxygenation in eight female and eight male healthy volunteers every fourth hour during a 24-h period. Parallel with MRI scans, standard urinary and plasma parameters were quantified. Significant circadian variations of total renal blood flow were found over 24 h, with increasing flow from noon to midnight and decreasing flow during the night. In contrast, no circadian variation in intrarenal oxygenation was detected. Urinary excretions of electrolytes, osmotically active particles, creatinine, and urea all displayed circadian variations, peaking during the afternoon and evening hours. In conclusion, total renal blood flow and kidney function, as estimated from excretion of electrolytes and waste products, display profound circadian variations, whereas intrarenal oxygenation displays significantly less circadian variation.

Noninvasive methods of magnetic resonance imaging (MRI) can quantify parameters of kidney function. The main purpose of this study was to determine baseline values of such parameters in healthy volunteers. In 28 healthy volunteers (15 women and 13 men), arterial spin labeling to estimate regional renal perfusion, blood oxygen level-dependent transverse relaxation rate (R-2*) to estimate oxygenation, and apparent diffusion coefficient (ADC), true diffusion (D), and longitudinal relaxation time (T-1) to estimate tissue properties were determined bilaterally in the cortex and outer and inner medulla. Additionally, phase-contrast MRI was applied in the renal arteries to quantify total renal blood flow. The results demonstrated profound gradients of perfusion, ADC, and D with highest values in the kidney cortex and a decrease towards the inner medulla. R-2* and T-1 were lowest in kidney cortex and increased towards the inner medulla. Total renal blood flow correlated with body surface area, body mass index, and renal volume. Similar patterns in all investigated parameters were observed in women and men. In conclusion, noninvasive MRI provides useful tools to evaluate intrarenal differences in blood flow, perfusion, diffusion, oxygenation, and structural properties of the kidney tissue. As such, this experimental approach has the potential to advance our present understanding regarding normal physiology and the pathological processes associated with acute and chronic kidney disease.

MRI can provide information of renal physiological parameters in a safe, non-invasive and relatively fast way. In this study we determined baseline values for total (tRBF) and regional (rRBF) renal blood flow, regional oxygenation level (R2*), regional true (D) and apparent (ADC) diffusion and regional T1 in healthy volunteers using the MRI techniques of Phase Contrast (PC), Arterial Spin Labeling (ASL), Blood Oxygen Level Dependent R2* (BOLD), Diffusion Weighted Imaging (DWI) and T1. Measurements of ADC and T1 are of interest since they have been shown to correlate to the degree of fibrosis. 28 healthy volunteers (15 female, 13 male) were recruited and underwent a 3T MRI scan. Since no significant differences of the investigated biomarkers were found between the corresponding regions in the left and right kidney or between the genders, only mean values are presented. Average tRBF through the kidney was 503±138 ml/min and global perfusion was 312±87 ml/min/100 g. Good correlations were found between tRBF and body surface area, BMI, and kidney volume. For cortex, outer and inner medulla, rRBF values, measured by ASL, were 290±63, 91±14 and 42±16 ml/min/100 g, resp, R2* values (BOLD) were 16.5±1.1, 26.8±1.6, and 36.8±3.8 s−1 resp, ADC values (DWI) were 2.43±0.17, 2.14±0.19 and 2.01±0.19 ×10−3 mm2/s resp, D values (DWI) were 2.11±0.23, 1.86±0.18 and 1.71±0.20 ×10−3 mm2/s resp and T1 values were 1146±76, 1403±170, and 1512±205 ms, resp. Significant interregional differences were found between cortex, outer and inner medulla in all studied parameters. In conclusion, MRI provides reliable and robust biomarkers for assessment of kidney function in an acceptable acquisition time. Knowledge of normal values of such functional biomarkers in different regions of the kidney is inevitable before their use in research or in clinical practice. Correlation between tRBF and Body Surface Area, BMI and Kidney volume ROI positions for ASL, BOLD, DWI and T1 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Poster: ECR 2017 / C-2996 / Non-invasive determination of renal cortical, outer and inner medullary blood flow, oxygenation and diffusion in healthy volunteers using ASL, BOLD and DWI MRI by: Eckerbom1, E. Cox2, J. Weis1, P. Hansell1, I. Subasic1, F. Palm1, S. Francis2, P. Liss1; 1Uppsala/SE, 2Nottingham/UK

Purpose Due to the risks associated with using contrast media in patients with impaired renal function there is clearly a need for non‐invasive techniques measuring renal blood flow (RBF) and oxygenation. Current techniques include arterial spin labelling (ASL), blood oxygen level‐dependent (BOLD) magnetic resonance imaging (MRI) and phase contrast (PC). In addition to needing thorough validation, it is also important to know if RBF and oxygenation are influenced by circadian rhythm. Therefore, we determined total and regional RBF and regional oxygenation in healthy volunteers as a function of time of day using these MRI. Methods and Materials Total RBF was determined by PC in renal arteries, regional RBF by ASL and regional oxygenation by BOLD in 6 healthy volunteers every fourth hour for a total of 24 hours resulting in 6 repeated measurements in each individual. Results Average total RBF was 898±10 ml/min and 893±27 ml/min for right and left kidney, respectively, with a drop during evening‐night but with significant individual variations. Average cortical RBF was 289±7 and 274±8 ml/min/100g for right and left kidney, respectively, with highest values during the day and lowest values during the evening‐night. Cortical oxygenation was 52±1 and 49±1 ms for right and left kidney, respectively, with minimal circadian variation. Conclusion Non‐invasive MRI is able to quantify also substile changes in RBF. Furthermore, these results demonstrate that RBF is influenced by circadian variations which should be considered when designing future studies in order to elucidate the role of deranged RBF regulation for the development of kidney disease.

Poster: ECR 2014 / C-2264 / Evaluation of regional renal blood flow with non-invasive ASL measurements compared with Gadolinium in patients before renal nephrectomy by: Eckerbom1, E. Cox2, J. Weis1, S. Ladjavardi1, M. Haggman1, P. Hansell1, F. Palm3, S. Francis2, P. Liss1; 1Uppsala/SE, 2Nottingham/UK, 3Linkoping/SE

Renal blood flow is tightly controlled by at least two different intrinsic mechanisms, which should guarantee a stable blood flow. However, it is currently unknown if renal hemodynamics is influenced by circadian rhythm like many other tissues. Therefore, we measured total and cortical renal blood flow using completely non‐invasive magnetic resonance technique in six healthy male volunteers every fourth hour for a total of 24 hours (six measurements in total). Total renal blood flow was measured using standard phase contrast technique in renal arteries, whereas cortical renal blood flow was measured using the newly developed arterial spin‐labeling technique.Total renal blood flow averaged 13.3±1.4 and 13.0±1.0 ml/min for right and left kidney, respectively, with a circadian variation of 18±5 and 14±3%. Cortical renal blood flow in the right kidney averaged 323±17 ml/min/100g with a variation of 10±2% between the different measurements. None of these variations reached statistical significance.In conclusion, neither total nor cortical renal blood flows display circadian variations. Thus, circadian variations in renal hemodynamics seem less likely to affect the results from studies investigating renal blood flow and related parameters.

MR examinations (Achieva 3 T, Philips, Best, The Netherlands) were performed at five different occasions in a healthy volunteer (male 60 years) and in one renal cancer patient (male 78 years) with normal renal function (creatinine 88 μmol/L). Intravoxel incoherent motion (IVIM) coefficients D + D* were measured using respiratory-triggered diffusion-weighted spin-echo echo-planar imaging. Perfusion data of the patient were acquired using a saturation-recovery gradient-echo sequence and with the bolus of Gd-BOPTA (Multihance). D + D* were computed by monoexponential fitting of MR signal intensity attenuation versus b for b = 0, 50, 100, 150 s/mm2. Perfusion parameters were evaluated with “NordicICE” software. The map of D + D* was compared qualitatively with the perfusion map computed from the Gd scan. D + D* values of the cortex and medulla were in the range 2.3–2.7 and 1.1–1.6 × 10-3 mm2/s, respectively. In conclusion, in this pilot study a good qualitative relation between IVIM variables D + D* and renal perfusion has been found.

The interruption of blood flow results in impaired oxygenation and metabolism. This can lead to electrophysiological changes, functional impairment and symptoms in quick succession. Quantitative measures of organ perfusion, perfusion reserve and tissue oxygenation are crucial to assess normal tissue metabolism and function. Magnetic resonance imaging (MRI) provides a number of quantitative methods to assess physiology in the kidney. Blood oxygenation level-dependent (BOLD) MRI provides a method for the assessment of oxygenation. Blood flow to the kidney can be assessed using phase contrast MRI. Dynamic contrast-enhanced MRI and arterial spin labelling (ASL) provide methods to assess tissue perfusion, ASL using the magnetization of endogenous water protons and thus providing a non-invasive method to assess perfusion. The application of diffusion-weighted MRI allows molecular motion in the kidney to be measured. Novel techniques can also be used to assess oxygenation in the renal arteries and veins and, combined with flow measures, provide an estimation of oxygen metabolism. Magnetic resonance imaging provides a synergy of non-invasive techniques to study renal function and the demand for these techniques is likely to be driven by the incentive to avoid the use of contrast media, to avoid radiation and to avoid complications with intervention procedures.

Acute kidney injury (AKI) is associated with increased mortality in COVID-19 patients. Multiparametric MRI was performed to study renal perfusion, oxygenation and tissue structure in nineteen COVID-19 intensive care patients. Results are compared between patients with and without COVID-19 associated AKI, and with healthy volunteers (HV). Cortical perfusion was lower in COVID-19 compared to HVs (P=0.0002) with cortex and medullary perfusion lower in AKI compared to non-AKI (P<0.03). Correlations between cortex measures in COVID-19 showed T 1 was positively correlated with T 2 and ADC, and T 2 was positively correlated with ADC and T 2 * suggesting interstitial oedema resulting from inflammation.