Circadian variation in renal blood flow and kidney function in healthy volunteers monitored using non-invasive magnetic resonance imaging

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 non-invasively 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 using MRI, and relate the findings with urinary excretions of electrolytes and markers of kidney function.Phase Contrast imaging, Arterial Spin Labeling and Blood Oxygen Level DependentR2*-mapping were used to assess the total renal blood flow and regional perfusion,and intrarenal oxygenation in eight female and eight male healthy volunteers every fourth hour during a 24hperiod. Parallel with MRI scans, standard urinary and plasma parameters were quantified. Significant circadian variations of total renal blood flow were found over 24hwith 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

Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging: a prospective case control study

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 (R2*) 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

Consensus-based technical recommendations for clinical translation of renal BOLD MRI.

Harmonization of acquisition and analysis protocols is an important step in the validation of BOLD MRI as a renal biomarker. This harmonization initiative provides technical recommendations based on a consensus report with the aim to move towards standardized protocols that facilitate clinical translation and comparison of data across sites. We used a recently published systematic review paper, which included a detailed summary of renal BOLD MRI technical parameters and areas of investigation in its supplementary material, as the starting point in developing the survey questionnaires for seeking consensus. Survey data were collected via the Delphi consensus process from 24 researchers on renal BOLD MRI exam preparation, data acquisition, data analysis, and interpretation. Consensus was defined as ≥ 75% unanimity in response. Among 31 survey questions, 14 achieved consensus resolution, 12 showed clear respondent preference (65-74% agreement), and 5 showed equal (50/50%) split in opinion among respondents. Recommendations for subject preparation, data acquisition, processing and reporting are given based on the survey results and review of the literature. These technical recommendations are aimed towards increased inter-site harmonization, a first step towards standardization of renal BOLD MRI protocols across sites. We expect this to be an iterative process updated dynamically based on progress in the field

Assessment of Renal Physiology Using Functional MRI

Kidney injury is a major cause of morbidity and mortality throughout the world, leading to substantial individual suffering and to a heavy financial burden for the society. A large number of common conditions such as diabetes, hypertension, autoimmune diseases and infections are highly associated with kidney injury. Disturbances in renal perfusion and oxygenation are believed to be involved in the pathogenesis of kidney injury and are therefore of interest to investigate closely. Studies to further the understanding of kidney injury have previously most often involved invasive procedures or ionizing radiation which have limited studies in humans due to ethical reasons. Hence there is a need to explore and implement noninvasive, nonionizing techniques to carry out human studies of renal physiology in health and disease. This thesis aimed to do so using a number of novel, noninvasive magnetic resonance imaging (MRI) techniques.  In the first study of this thesis, we scanned the kidneys of healthy volunteers with noninvasive MRI and found significant differences between the renal cortex, inner and outer medulla regarding blood flow, oxygenation, water diffusion and tissue characteristics. In the second study we scanned the kidneys with MRI and collected urine from healthy volunteers every fourth hour for 24 hours and found circadian variations for total renal blood flow as well as for a number of urinary parameters. Renal oxygenation was stable with only small diurnal variations. In the third study we implemented the MRI techniques used in study 1 and 2 and one additional MRI technique in COVID-19 patients admitted to the intensive care unit for severe respiratory failure, with and without acute kidney injury (AKI). We found significantly reduced total renal blood flow as well as  cortical and medullary perfusion in patients with AKI compared to patients without AKI. No significant difference was found between the two groups regarding renal oxygenation, water diffusion or tissue characteristics. In the fourth study we used the same MRI techniques as in study 3 to follow up patients previously treated for severe COVID-19 without and with different degrees of AKI. We found significantly reduced apparent diffusion coefficient (ADC) and total renal blood flow in patients that had high grade AKI compared to patients that did not have AKI during hospitalization for COVID-19. No significant difference regarding oxygenation was found between the groups. In conclusion, this thesis shows that it is possible to use multiparametric noninvasive MRI for renal studies in clinical practice.

Assessment of Renal Physiology Using Functional MRI

Kidney injury is a major cause of morbidity and mortality throughout the world, leading to substantial individual suffering and to a heavy financial burden for the society. A large number of common conditions such as diabetes, hypertension, autoimmune diseases and infections are highly associated with kidney injury. Disturbances in renal perfusion and oxygenation are believed to be involved in the pathogenesis of kidney injury and are therefore of interest to investigate closely. Studies to further the understanding of kidney injury have previously most often involved invasive procedures or ionizing radiation which have limited studies in humans due to ethical reasons. Hence there is a need to explore and implement noninvasive, nonionizing techniques to carry out human studies of renal physiology in health and disease. This thesis aimed to do so using a number of novel, noninvasive magnetic resonance imaging (MRI) techniques.  In the first study of this thesis, we scanned the kidneys of healthy volunteers with noninvasive MRI and found significant differences between the renal cortex, inner and outer medulla regarding blood flow, oxygenation, water diffusion and tissue characteristics. In the second study we scanned the kidneys with MRI and collected urine from healthy volunteers every fourth hour for 24 hours and found circadian variations for total renal blood flow as well as for a number of urinary parameters. Renal oxygenation was stable with only small diurnal variations. In the third study we implemented the MRI techniques used in study 1 and 2 and one additional MRI technique in COVID-19 patients admitted to the intensive care unit for severe respiratory failure, with and without acute kidney injury (AKI). We found significantly reduced total renal blood flow as well as  cortical and medullary perfusion in patients with AKI compared to patients without AKI. No significant difference was found between the two groups regarding renal oxygenation, water diffusion or tissue characteristics. In the fourth study we used the same MRI techniques as in study 3 to follow up patients previously treated for severe COVID-19 without and with different degrees of AKI. We found significantly reduced apparent diffusion coefficient (ADC) and total renal blood flow in patients that had high grade AKI compared to patients that did not have AKI during hospitalization for COVID-19. No significant difference regarding oxygenation was found between the groups. In conclusion, this thesis shows that it is possible to use multiparametric noninvasive MRI for renal studies in clinical practice.

Consensus-based technical recommendations for clinical translation of renal BOLD MRI.

Harmonization of acquisition and analysis protocols is an important step in the validation of BOLD MRI as a renal biomarker. This harmonization initiative provides technical recommendations based on a consensus report with the aim to move towards standardized protocols that facilitate clinical translation and comparison of data across sites. We used a recently published systematic review paper, which included a detailed summary of renal BOLD MRI technical parameters and areas of investigation in its supplementary material, as the starting point in developing the survey questionnaires for seeking consensus. Survey data were collected via the Delphi consensus process from 24 researchers on renal BOLD MRI exam preparation, data acquisition, data analysis, and interpretation. Consensus was defined as ≥ 75% unanimity in response. Among 31 survey questions, 14 achieved consensus resolution, 12 showed clear respondent preference (65-74% agreement), and 5 showed equal (50/50%) split in opinion among respondents. Recommendations for subject preparation, data acquisition, processing and reporting are given based on the survey results and review of the literature. These technical recommendations are aimed towards increased inter-site harmonization, a first step towards standardization of renal BOLD MRI protocols across sites. We expect this to be an iterative process updated dynamically based on progress in the field

Consensus-based technical recommendations for clinical translation of renal BOLD MRI.

Harmonization of acquisition and analysis protocols is an important step in the validation of BOLD MRI as a renal biomarker. This harmonization initiative provides technical recommendations based on a consensus report with the aim to move towards standardized protocols that facilitate clinical translation and comparison of data across sites. We used a recently published systematic review paper, which included a detailed summary of renal BOLD MRI technical parameters and areas of investigation in its supplementary material, as the starting point in developing the survey questionnaires for seeking consensus. Survey data were collected via the Delphi consensus process from 24 researchers on renal BOLD MRI exam preparation, data acquisition, data analysis, and interpretation. Consensus was defined as ≥ 75% unanimity in response. Among 31 survey questions, 14 achieved consensus resolution, 12 showed clear respondent preference (65-74% agreement), and 5 showed equal (50/50%) split in opinion among respondents. Recommendations for subject preparation, data acquisition, processing and reporting are given based on the survey results and review of the literature. These technical recommendations are aimed towards increased inter-site harmonization, a first step towards standardization of renal BOLD MRI protocols across sites. We expect this to be an iterative process updated dynamically based on progress in the field

Hypertriglyceridemic waist may explain ethnic differences in hypertension among patients with type 2 diabetes in Sweden

<p>Abstract</p> <p>Background</p> <p>Hypertension is common among persons with type 2 diabetes. The aim of this study was to analyze the association between ethnicity and hypertension prevalence after adjusting for age, sex, Hba1c, total cholesterol, elevated triglycerides and hypertriglyceridemic waist. The study population consisted of 354 primary health care patients diagnosed with type 2 diabetes (173 Assyrians/Syrians and 181 Swedes) residing in Södertälje, Sweden. Unconditional logistic regression was used to analyze the data.</p> <p>Results</p> <p>Hypertension prevalence was higher among Swedes than Assyrians/Syrians, (77% versus 58%; p = 0.001). In the unadjusted logistic regression model, the odds ratio for hypertension in Swedes was twice as high than that in Assyrians/Syrians (OR = 2.44; 95% CI =1.54-3.86). In the age- and sex-adjusted model, odds ratio of hypertension was 2.25 (95% CI 1.41-3.60). After adjustments for total cholesterol was made, the odds ratio of hypertension decreased slightly to 1.73. When elevated triglycerides and hypertriglyceridemic waist were separately introduced, the odds ratio of hypertension was no longer significant between the ethnic groups (1.60 and 1.43 for triglycerides and hypertriglyceridemic waist respectively). In addition, advanced age – 60–69 years old (OR = 1.80, CI 95% 1.00-3.20) and ≥ 70 years old (OR = 2.88, CI 95% 1.40-5.93), elevated total cholesterol (OR = 1.48, CI 95% 1.12-1.95) and presents of hypertriglyceridemic waist (those with high WC and high TG) were significant confounding factors for the increased risk of hypertension independent of ethnicity.</p> <p>Conclusions</p> <p>The crude differences in prevalence of hypertension between the Swedes and Assyrians/Syrians in our study population with type 2 diabetes were no longer significant when adjusting for high triglycerides levels or the presence of hypertriglyceridemic waist.</p