| 1. |
- Eckerbom, Per, 1974-, et al.
(författare)
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Circadian variation in renal blood flow and kidney function in healthy volunteers monitored with noninvasive magnetic resonance imaging
- 2020
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 319:6, s. F966-F978
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Tidskriftsartikel (refereegranskat)abstract
- 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 (R2*) 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.
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| 2. |
- Eckerbom, Per, 1974-, et al.
(författare)
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Multiparametric assessment of renal physiology in healthy volunteers using noninvasive magnetic resonance imaging
- 2019
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 316:4, s. F693-F702
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive 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 females, 13 males), Arterial Spin Labeling (ASL) to estimate regional renal perfusion, Blood Oxygen Level Dependent (BOLD) transverse relaxation rate (R2*) to estimate oxygenation, and Apparent Diffusion Coefficient (ADC), true diffusion (D) and longitudinal relaxation time (T1) to estimate tissue properties were determined bilaterally in the cortex, outer and inner medulla. Additionally, phase contrast (PC) 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. R2* and T1 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 females and males. In conclusion, non-invasive MRI provides useful tools to evaluate intra renal 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 current understanding regarding normal physiology and the pathological processes associated with acute and chronic kidney disease.
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| 3. |
- Luther, Tomas, et al.
(författare)
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Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging : a prospective case control study
- 2022
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Ingår i: Critical Care. - : Springer Nature. - 1364-8535 .- 1466-609X. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- Renal hypoperfusion has been suggested to contribute to the development of acute kidney injury (AKI) in critical COVID-19. However, limited data support this. In this prospective case-control study we aimed to investigate differences in renal perfusion, oxygenation and water diffusion using multiparametric magnetic resonance imaging (mpMRI) in critically ill COVID-19 patients with and without AKI. Nineteen patients without prior kidney disease treated in intensive care for respiratory failure were examined. Ten patients had AKI and nine patients did not have AKI using Kidney Disease: Improving Global Outcomes Creatinine criteria. 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/100g/min, P = 0.015) and medulla (28 [18-47] vs. 47 [38-73] mL/100g/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.). We conclude that in critically ill COVID-19 patients with AKI, the total, cortical and medullary renal blood flow are reduced compared with similar patients without AKI, whereas no differences in renal oxygenation were demonstrable in this setting.
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| 4. |
- Luther, Tomas, et al.
(författare)
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Plasma expansion and renal perfusion in critical COVID-19 with AKI: a prospective case control study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: A decrease in renal perfusion during acute kidney injury (AKI) due to critical COVID-19 have 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 7.5ml/kg Ringer’s Acetate (Baxter). Mean arterial pressure (MAP) was recorded before plasma infusion and compared with maximum value after. 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 18 mmHg (CI 8-28) and 20 mmHg (CI 10-31) in patients with and without AKI respectively. Total renal perfusion and cortical perfusion was not significantly changed by plasma expansion in either group. There were however there was a reduction of medullary perfusion in patients without AKI from 55 (CI 39-79) to 34 (CI 24-48) ml/min/100g (P = 0.0027).Conclusion: Plasma expansion with a standardized fluid bolus did not increase renal perfusion in critically ill patients with COVID-19.
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| 5. |
- Palm, Fredrik, et al.
(författare)
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Reduced nitric oxide in diabetic kidneys due to increased hepatic arginine metabolism : implications for renomedullary oxygen availability
- 2008
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 294:1, s. F30-7
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Tidskriftsartikel (refereegranskat)abstract
- Nitric oxide (NO) is a potent regulator of both vascular tone and oxygen utilization. Diabetes is commonly associated with both NO deficiency and reduced renomedullary oxygen availability. Arginine availability as regulator of NO production has gained growing interest. We hypothesized that arginine limitation causes diabetes-induced renomedullary NO deficiency, which directly influences renomedullary oxygen tension (P(o2)). Medullary NO, P(o2), and blood flow were measured in control and streptozotocin-induced diabetic rats, which were treated or not treated with alpha-tocopherol, and administered l-arginine followed by N(omega)-nitro-l-arginine methyl ester. Major components of arginine metabolism were also investigated. Diabetic rats had reduced renomedullary NO levels compared with controls. Arginine selectively increased NO levels in diabetic rats and totally restored NO levels in alpha-tocopherol-treated animals. Tocopherol prevented the reduction in medullary P(o2) in the diabetic animals. Although blood flow increased equally in all groups, arginine increased P(o2) exclusively in the diabetic groups. Diabetes decreased plasma arginine and asymmetric dimethylarginine concentrations, but increased hepatic CAT-2A and plasma ornithine independently of alpha-tocopherol treatment. In conclusion, diabetic rats had reduced renomedullary NO due to decreased plasma arginine following increased hepatic arginine uptake and degradation. This was unrelated to oxidative stress. The diabetes-induced reduction in renomedullary P(o2) was restored by either acute arginine administration, which also restored NO levels, or long-term antioxidant treatment. Arginine increased medullary NO and P(o2) independently of altered hemodynamics in the diabetic groups. This reveals a direct regulatory function of NO for renomedullary P(o2) especially during situations of elevated oxidative stress.
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| 6. |
- Alhuseinalkhudhur, Ali, et al.
(författare)
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Human Epidermal Growth Factor Receptor 2-Targeting [68Ga]Ga-ABY-025 PET/CT Predicts Early Metabolic Response in Metastatic Breast Cancer.
- 2023
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 64:9, s. 1364-1370
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Tidskriftsartikel (refereegranskat)abstract
- Imaging using the human epidermal growth factor receptor 2 (HER2)-binding tracer 68Ga-labeled ZHER2:2891-Cys-MMA-DOTA ([68Ga]Ga-ABY-025) was shown to reflect HER2 status determined by immunohistochemistry and in situ hybridization in metastatic breast cancer (MBC). This single-center open-label phase II study investigated how [68Ga]Ga-ABY-025 uptake corresponds to biopsy results and early treatment response in both primary breast cancer (PBC) planned for neoadjuvant chemotherapy and MBC. Methods: Forty patients with known positive HER2 status were included: 19 with PBC and 21 with MBC (median, 3 previous treatments). [68Ga]Ga-ABY-025 PET/CT, [18F]F-FDG PET/CT, and core-needle biopsies from targeted lesions were performed at baseline. [18F]F-FDG PET/CT was repeated after 2 cycles of therapy to calculate the directional change in tumor lesion glycolysis (Δ-TLG). The largest lesions (up to 5) were evaluated in all 3 scans per patient. SUVs from [68Ga]Ga-ABY-025 PET/CT were compared with the biopsied HER2 status and Δ-TLG by receiver operating characteristic analyses. Results: Trial biopsies were HER2-positive in 31 patients, HER2-negative in 6 patients, and borderline HER2-positive in 3 patients. The [68Ga]Ga-ABY-025 PET/CT cutoff SUVmax of 6.0 predicted a Δ-TLG lower than -25% with 86% sensitivity and 67% specificity in soft-tissue lesions (area under the curve, 0.74 [95% CI, 0.67-0.82]; P = 0.01). Compared with the HER2 status, this cutoff resulted in clinically relevant discordant findings in 12 of 40 patients. Metabolic response (Δ-TLG) was more pronounced in PBC (-71% [95% CI, -58% to -83%]; P < 0.0001) than in MBC (-27% [95% CI, -16% to -38%]; P < 0.0001), but [68Ga]Ga-ABY-025 SUVmax was similar in both with a mean SUVmax of 9.8 (95% CI, 6.3-13.3) and 13.9 (95% CI, 10.5-17.2), respectively (P = 0.10). In multivariate analysis, global Δ-TLG was positively associated with the number of previous treatments (P = 0.0004) and negatively associated with [68Ga]Ga-ABY-025 PET/CT SUVmax (P = 0.018) but not with HER2 status (P = 0.09). Conclusion: [68Ga]Ga-ABY-025 PET/CT predicted early metabolic response to HER2-targeted therapy in HER2-positive breast cancer. Metabolic response was attenuated in recurrent disease. [68Ga]Ga-ABY-025 PET/CT appears to provide an estimate of the HER2 expression required to induce tumor metabolic remission by targeted therapies and might be useful as an adjunct diagnostic tool.
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| 7. |
- Friederich, Malou, et al.
(författare)
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Uncoupling protein-2 in diabetic kidneys : increased protein expression correlates to increased non-transport related oxygen consumption
- 2008
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Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer Berlin/Heidelberg. - 0065-2598 .- 2214-8019. ; 614, s. 37-43, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic patients have an elevated risk to develop renal dysfunction and it has been postulated that altered energy metabolism is involved. We have previously shown that diabetic rats have markedly decreased oxygen availability in the kidney, resulting from increased oxygen consumption. A substantial part of the increased oxygen consumption is unrelated to tubular transport, suggesting decreased mitochondrial efficiency. In this study, we investigated the protein expression of mitochondrial uncoupling protein (UCP)-2 in kidney tissue from control and streptozotocin (STZ)-induced diabetic rats. Protein levels of UCP-2 were measured in adult male control and STZ-diabetic Wistar Furth as well as Sprague Dawley rats in both the kidney cortex and medulla by Western blot technique. Two weeks of hyperglycemia resulted in increased protein levels of UCP-2 in kidneys from both Wistar Furth and Sprague Dawley rats. Both cortical and medullary UCP-2 levels were elevated 2-3 fold above control levels. We conclude that sustained STZ-induced hyperglycemia increases the kidney levels of mitochondrial UCP-2, which could explain the previously reported increase in non-transport related oxygen consumption in diabetic kidneys. The elevated UCP-2 levels may represent an effort to reduce the increased production of superoxide radicals which is evident during diabetes.
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| 8. |
- Luther, Tomas
(författare)
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Aspects of renal blood flow and oxygenation in acute kidney injury during severe infections
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Acute kidney injury (AKI) is a common complication in patients treated in the intensive care unit (ICU). Severe infections/sepsis is the most common aetiology, and about half of patients treated in the ICU due to sepsis are affected. Although AKI often resolves over time, the development of AKI decreases the chances of surviving. This thesis aims to investigate mechanisms of AKI development related to renal blood flow and oxygenation, by using both animal experiments and novel techniques available to examine patients.In Paper I, anaesthetised sheep were randomised to receive a bacterial infusion for 29 hours, or serve as controls. Isolated mitochondria from the animals’ renal cortex were investigated in vitro, at the beginning, and at the end of the experiment. Renal function deteriorated significantly in sheep with sepsis compared with the controls, and mitochondrial dysfunction by sepsis, comprised of a reduction of the RCR and an increased CII/CI-relation in State 3, was demonstrated in the sepsis group at the end of the experiment. However, renal cortical mitochondrial efficiency and uncoupling was unaffected by sepsis and cannot explain the discrepancy between oxygen consumption and tubular transport.Paper II described and characterised AKI during the novel infection COVID-19, in a prospective cohort study of 57 patients in the ICU. Biomarkers for renal damage were measured in urine from 52 of the study participants. The results show that 89% of the study participants developed AKI. Oliguria was common and occurred early after ICU admission. The biomarkers in the urine were generally elevated, however, with only minor differences between patients stratified by severity of AKI.In Paper III, 19 patients in the ICU due to COVID-19 were examined with magnetic resonance imaging (MRI). Renal blood flows, oxygenation, and water content were measured. The results show that patients with AKI had lower renal blood flows, both in the cortex and medulla, compared with those without. However, no differences regarding oxygenation or water content was demonstrated.Paper IV investigated whether plasma expansion could affect renal blood flows in 17 of the study participants in Paper III. Ringer‘s acetate (7.5 ml/kg) was infused and the measurement with the magnetic camera was repeated. The results show that renal blood flows did not increase, either in patients with or without AKI, even though the increase in circulating blood volume resulted in higher blood pressure. However, patients without AKI had a lower perfusion in the renal medulla after plasma expansion.
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| 9. |
- Morcos, Sameh K., et al.
(författare)
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Reducing the risk of iodine-based and MRI contrast media administration : recommendation for a questionnaire at the time of booking
- 2008
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Ingår i: European Journal of Radiology. - : Elsevier BV. - 0720-048X .- 1872-7727. ; 66:2, s. 225-229
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a practical questionnaire to be used when a contrast medium examination is requested. The questionnaire is based on the guidelines from the European Society of Urogenital Radiology. Its aim is to identify patients at increased risk of clinically relevant renal and non-renal adverse reactions to iodine-based and MRI contrast agents. The questionnaire should be completed by the referring physician when the examination is requested.
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| 10. |
- Nordquist, Lina, et al.
(författare)
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Hypoxia in the diabetic kidney is independent of advanced glycation end-products.
- 2013
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Ingår i: Advances in Experimental Medicine and Biology. - New York, NY : Kluwer Academic Publishers. - 0065-2598 .- 2214-8019. ; 765, s. 185-193
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Tidskriftsartikel (refereegranskat)abstract
- Sustained hyperglycemia is closely associated with increased risk to develop nephropathy. We have previously reported alterations in the intrarenal oxygen metabolism already after the early onset of diabetes. Furthermore, formation of advanced glycation end-products (AGE) is postulated as a major contributor to diabetic nephropathy. We therefore investigated the possible relationship between altered oxygen metabolism and AGE in diabetic kidneys.Normoglycemic and streptozotocin-diabetic rats with and without chronic treatment with aminoguanidine (AGE inhibitor; 600 mg/kg bw/24 h in drinking water) or L-N(6)-(1-Iminoethyl)lysine (L-NIL, iNOS inhibitor, 1 mg/kg bw/24 h in drinking water) were studied 2 weeks after induction of diabetes. Glomerular filtration rate (GFR) was estimated by inulin clearance, oxygen tension (pO(2)) and interstitial pH by microelectrodes and regional renal blood flow (RBF) by laser-Doppler. Histological changes were evaluated on fixed tissue.Glomerular hyperfiltration was unaffected by aminoguanidine, whereas L-NIL normalized GFR in diabetic rats. pO(2) and interstitial pH, but not RBF, were lower in both kidney cortex and medulla compared to control rats, but was unaffected by both chronic treatments. Urinary protein excretion was higher in diabetic rats and unaffected by L-NIL, whereas aminoguanidine paradoxically increased this parameter. Damage scores were similar in all groups.In conclusion, diabetes-induced alterations in intrarenal oxygen metabolism are independent of the AGE pathway, and precede any morphological changes. These findings highlight the early stage of diabetes as being a metabolic disorder also in the kidney.
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