Freitag, 02.10.2020

14:00 - 15:30

Poster DGfN 2020

Chronisches Nierenversagen 1 (P017 - P025; LA06)

 
Einfluss der Hypervolämie auf die Immunfunktion bei CKD5D-Patienten
P017 

A. Wilke, N. Schleicher, C. Ulrich, M. Girndt, R. Fiedler; Halle (Saale)

Hintergrund: Über Signalkaskaden wird eine NLRP3 Inflammasom-Aktivierung mit Produktion inflammatorischer Zytokine ausgelöst. Als Ursache wird eine Endotoxämietranslokation über die geschädigte Darmmukosa in hypervolämen Patienten diskutiert. Wir untersuchten daher, inwiefern eine Hypervolämie in CKD5D-Patienten einen Anstieg an entzündlichen Monozyten triggert, die ihrerseits, vermittelt über reaktive Sauerstoffspezies (ROS), eine NLRP3 Inflammasom-Aktivierung mit anschließender Caspase-1 vermittelter IL-ß-Ausschüttung verursachen.
Methode: In einer Beobachtungsstudie mit 45 CKD5D-Patienten wurden Zellzahlen von Mono- und Lymphozyten, Caspase-1-Aktivität sowie IL-1ß-Gehalt des Serums vor- und nach interdialytischen Intervall bestimmt. Als mögliche Ursache einer NLRP3 Inflammasom-Aktivierung wurden mitochondriale und zytoplasmatische ROS in PBMC der Patienten ermittelt. Die Funktionalität der Inflammasomaktivierung wurde mittels in vitro Stimulation von PBMC simuliert. Der Hydratationsstatus wurde mittels Bioimpedanzmethode bestimmt, eine Vektorperzentile >75 galt als hypervoläm (H) und <75 als normovoläm (N).
Ergebnisse: 17 Patienten wurden als H, 19 als N klassifiziert. 9 Patienten erfüllten die Einschlusskriterien nicht. Die Monozytenzahlen waren bei H-HD erhöht, die Lymphozytenzahlen hingegen erniedrigt. ROS war leicht, jedoch nicht signifikant erhöht bei H-HD. Jedoch war weder die Frequenz der Caspase-1-positiven Monozyten (Mediane Fluoreszenzintensität H:77,9±4,2% vs. N:79,2±6,9%; p=0,916) noch die Caspase-1- Expression (H:42,8±13,3 vs. N:43,6±17,1, p=0,880) in beiden Kollektiven unterschiedlich. Eine in vitro Stimulation mit spezifischen NLRP3 Inflammasom-aktivierenden Agenzien (LPS/Nigericin) führte zur Erhöhung der Frequenz der Caspase-1-positiven Monozyten (H:89,9±22,6% vs. N:88,0±23,3%, p=0,900). IL-1ß als Haupt-Read-out einer NLRP3 Inflammasom-Aktivierung war weder auf mRNA- (H:1,7±1,9 vs. N:1,1±0,8; p=0,306) noch auf Proteinebene (pg/ml) (H:1,99±0,2 vs. N:1,98±0,6; p<0,135) unterschiedlich.

P017-1
P017-2


Zusammenfassung: Unsere Daten geben keine Hinweise, dass durch Hypervolämie getriggerte Prozesse zu einer Aktivierung des NLRP3 Inflammasoms führen. Damit scheint der Verdacht, dass eine verdeckte Endotoxämietranslokation als mögliche Ursache einer Hypervolämie, die letztendlich auch zu einer verstärkten Inflammsomaktivierung führen müsste, widerlegt.

 
Galectin-3 strongly associates with renal function, cardiomyopathy and fibrosis in patients with Fabry disease
P018 

C. Drechsler, R. de Boer, D. Oder, L. Gutjahr-Lengsfeld, N. Üçeyler, C. Sommer, C. Wanner, P. Nordbeck; Würzburg, Groningen/NL

Objective: Patients with Fabry disease frequently develop cardiac hypertrophy and progressive Fabry nephropathy. The progress of cardiac hypertrophy can lead to replacement fibrosis and heart failure. Galectin-3 is expressed in the heart, kidneys, blood vessels, and macrophages. It marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Experimental data suggest that galectin-3 is involved in fibrosis and inflammation also associated with renal failure. Galectin-3 inhibitor therapy tested in a phase 2 clinical trial in chronic kidney disease lead to an improvement of the estimated glomerular filtration rate. Given the role of Galectin-3 in cardiac hypertrophy, heart and renal failure, we hypothesized that it may be of potential relevance particularly for Fabry disease patients.
Method: This study investigated the galectin-3 concentrations in 172 patients with genetically proven Fabry disease. We studied the association of galectin-3 concentrations with renal function, left ventricular mass, and adverse clinical symptoms in patients with Fabry disease. Galectin-3 was measured by FDA-approved ELISA. GFR was determined by DTPA clearance. Left ventricular mass and cardiomyopathy were assessed by magnetic resonance imaging and echocardiography. In cross-sectional analysis, associations with adverse clinical outcomes were determined by correlation analysis and linear and binary logistic regression analysis, respectively. Data was adjusted for age and sex.
Results: Patients had a mean age of 39±14 years and 41% were male. The mean galectin-3 concentration was 17±12 ng/mL (normal value is approx. 11 ng/mL). Patients had a mean BMI of 23.7±4.5 kg/m2 and a mean GFR of 92±38 ml/min. Galectin-3 was strongly correlated with GFR, creatinine and urea. With higher galectin-3 concentrations of the patients, their GFR was lower (r=-0.63, p<0.001) and creatinine and urea were higher (r=0.68 and r=0.53, respectively, both p<0.001). Furthermore, cardiac hypertrophy was significantly higher with higher concentrations of galectin-3. The correlation coefficient for septal hypertrophy was r=0.43 (p<0.001) and for posterior hypertrophy r=0.39 (p<0.001), respectively. Similarly, cardiac fibrosis was significantly higher with higher galectin-3 levels (r=0.34, p<0.001). Patients of the highest galectin-3 tertile furthermore had significantly higher risks of adverse clinical symptoms. The adjusted odds ratio to suffer from angina pectoris was increased > 6-fold and the odds ratio to suffer from neuropathic pain was increased > 3-fold for patients of the highest galectin-3 tertile as compared to patients of the lowest galectin-3 tertile.
Conclusion: Increased galectin-3 concentrations were strongly associated with cardiac hypertrophy, cardiac fibrosis, decreased renal function, and adverse clinical symptoms in patients with Fabry disease. Galectin-3 can be useful as biomarker for cardiac and renal complications in Fabry disease. Galectin-3 inhibitor treatment may reduce complications of Fabry disease, and requires a randomized controlled trial.

 
Effect of High Dose Vitamin D Therapy on the Development of Hungry Bone Disease after Parathyroidectomie in Patients with CKD Stage 5
P019 

M. Grube, F. Weber, A. L. Kahl, N. Mülling, W. Reinhardt; Essen

Objective: Parathyroidectomie (PTx) is the treatment of choice in patients with severe secondary hyperparathyroidism in patients with end stage kidney disease (CKD Stage 5).The period after PTx is often associated with a profound hypocalcemic state, as the result from the immediate stop of bone resorption to bone formation, commonly known as “hungry bone disease”. This period very often requires high doses of calcium, mostly via the i.v. route and the hospital stay is often extended.
We were interested in the effect of the administration of high dose of active Vitamin D on the biochemical bone parameters in the postoperative course after PTx up to ten weeks.
Method: 67 patients (mean age: 46.8 years; all on the waiting list for kidney transplantation, underwent subtotal PTx and were prospectively evaluated. Bone specific parameters (Serum Total Ca, Albumin corrected Ca, PTH, PO4, AP) were measured daily and after one week in weekly intervals up to ten weeks after PTx.
All patients received 12 ug Alfacalcidol and Ca-Acetat 8.850 mg on the day of surgery and on day 1-2 after PTx. Then, the dose of Alfacalcidol was adapted to a mean dose of 4 ug after 6 weeks and Ca-Acetat could be reduced to a mean dose of 4.5 gm/day after 6 weeks.
Results: PTH decreased from (median) 1375 to18 pg/ml (p< 0.001) and stabilized to 39.8 pg/ml after 6 weeks.
Ca dropped significantly (mean +/-SD) 2.39+/-0.24 to 1.93 +/-0.21 mmol/l  (p<0.01) on the first postoperative day and stabilized to 2.14 after 10 days.
Severe hypocalcemia (Ca <1.5 mmol/l) was found transiently in 8.5 % of the patients; only 7.6 % required i.v. Calcium administration. Hypercalcemia (Ca > 2.6 mmol/l) occurred in 14 % mostly within the third week pop. AP fell from a median 134 U/L to 121 U/l (p<0.01) and increased again to 196 U/L (max. 1400 U/l) (p<0.001) after 2 weeks and stabilized finally to 158 U/l. The pretreatment of Cinacalcet (65%) had no effect on the bone parameters.
Conclusion: The period after PTx in CKD stage 5 patients is characterized by the presumed Calcium drop within the first days. Ongoing high turnover is observed in the 2nd and 3rd week. By the administration of high dose of alfacalcidol and Ca-Acetat the episodes of severe hypocalcemia and the requirement of i.v. Calcium is far less pronounced compared to previous studies.

 
Urine complement fragments are associated with kidney function and disease etiology
P020 

R. Wendt, H. Mischak, T. He, I. Golovko, J. Siwy, J. Beige; Leipzig, Hannover

Objective: The complement system is increasingly recognized as an important mediator of various kidney diseases. The kidney seems particularly susceptible to complement-mediated injury. Studies on complement excretion in urine are scarce and might add important non-interventional information on complement activation in different diseases.
Method: For this study urinary proteome data stored in the Human Urine Proteome Database (n=70.000)obtained by capillary electrophoresis coupled to mass spectrometry (CE-MS) were assessed upon availbility of renal diagnosis and function data. In addition, patients from the retrospective EU-funded PersTIgAN project (n=207) were included to investigate course of renal function in IgAN associated to certain complement peptides.
Results: Most frequent and representative peptides derived from all-peptides analyses (n=7087) with renal data were fragments e12939 and e12606, representative for C3 and CFB, resp.. Clusters of representative relative C3 and CFB peptide excretion in different diseases are shown in Figure after normalization of peptide abundance vs. ADPKD (a non-immune entity).

P020

In IgAN (Perstigan cohort, n=207), e12939 (C3) was significantly higher (p=0.04) in a that third of patients with the highest GFR loss within 1 yr follow-up compared to the third with the lowest GFR loss.
Conclusion: There was a remarkable high excretion of complement fragments, mainly C3, in membranous nephropathy, lupus nephritis, focal segmental glomerulosclerosis, IgAN but minmal change disease and diabetic nephropathy as well. In contrast, there was little complement excretion in ADPKD, non-renal SLE and non-nephropathic diabetes. The data suggest that glomerular filtration is not likely to explain the majority of the observed excretions. Complement excretions might be mirroring some of the processes at the cellular or circulation level and point attention to future molecular analyses.

 
Proteomic Characterization of Obesity-related Nephropathy
P021 

R. Wendt, T. He, J. Siwy, A. Latoszinska, J. Beige, H. Mischak; Leipzig, Hannover

Objective: Systematic insight into the pathogenesis and epidemiology of nephropathy related to obesity without diabetes is rather limited. There are patients showing a clinical context of obesity and nephropathy without having diabetes, pointing to a hypothetic consideration of “obesity-related nephropathy” (ORN), a condition which currently is not defined and requires exclusion of diabetes before defining it. This work reaches out to investigate impact of BMI on urinary proteome and to characterize yet non-specified peptide patterns in urine that may be indicative of ORN and may indicate possible molecular mechanisms of ORN pathophysiology.
Method: For this study urinary proteome data stored in the Human Urine Proteome Database obtained by capillary electrophoresis coupled to mass spectrometry (CE-MS) were assessed. Underlying kidney disease was known with regard to presence or absence of diabetes and nephropathy (n=1435). To generate a classifier potentially indicating ORN, multiple peptides significantly associated with obesity and reduced kidney function were combined using support vector machines (SVM).
Results: 365 peptides showed associations with BMI with association strengths ranging from R=0.1 to 0.28 (p<0.01). The 10 most significant peptides are specific collagen fragments, most of them from collagen type I, and are reduced with increasing BMI. 458 peptides also showed association with eGFR, albeit with opposing trend to BMI. By combining BMI and GFR indicative peptides, a classifyer was developed with an ROC-accuracy of 0,929 (95% CI 0.846 to 0.975) (Figure) to identify patients with CKD and BMI > 27 without regard to diabetes.

P021-1
P021-2


Conclusion: These analyses in a huge cohort of urine samples from patients with known eGFR, BMI and diabetes status showed a complex multi-level association between peptide fragments with renal risk in obesity. Most peptides associated with GFR and BMI belonged to the collagen superfamily and were inversely associated with BMI but directly with eGFR.
This concordant observation indicates a reduction of collagen degradation with increasing BMI and/or reduced kidney function. It is tempting to speculate that collagen homeostasis along with body mass on one hand, and kidney function on the other, are substantially interconnected.

 
The ‘lung-kidney interaction’ in patients with COPD: a high risk constellation
P022 

S. Schunk, C. Beisswenger, F. Ritzmann, C. Herr, M. Wagner, S. Triem, G. Hütter, D. Schmit, T. Sarakpi, S. Zewinger, A. Honecker, P. Boor, R. Jörgs, H. Watz, C. F. Vogelmeier, R. Bals, D. Fliser, T. Speer; Homburg/Saar, Aachen, München, Marburg

Objective: Chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) represent global public health problems and are associated with high disease-related morbidity and mortality. However, it is unclear whether the presence of CKD aggravates the clinical course of COPD and vice versa.
Method: A preclinical murine model of cigarette smoke (CS)-induced lung injury was combined with an established CKD model (adenine nephropathy). In 2,314 patients with stable COPD enrolled in the prospective multi-centre COSYCONET study, urinary Dickkopf-3 (DKK3), a renal tubular cell-derived stress marker, was quantified. Over a median follow-up of 37.1 months the association between urinary DKK3 and trajectories of forced expiratory pressure in 1 second (FEV1) and estimated glomerular filtration rate (eGFR), exercise capacity, risk of COPD exacerbation, and mortality was determined.
Results: In the animal model, CKD was associated with higher systemic and pulmonary inflammation compared to CS alone, and the combination of CKD and CS significantly aggravated kidney fibrosis and increased renal expression of DKK3. In COPD patients from COSYCONET, higher urinary DKK3 was associated with more rapidly declining FEV1 during follow-up (OR 3.36, 95% CI 2.22-5.08), higher risk for COPD exacerbation (OR 1.24, 95% CI 1.03-1.50), lower 6-minute walking distance, and higher all-cause mortality (HR 1.49, 95% CI 1.08-2.05). Importantly, higher urinary DKK3 was also associated with declining eGFR during follow-up (OR 2.23, 95% CI 1.22-4.07). These results were confirmed using a machine learning approach. Neither eGFR nor proteinuria was associated with lung or kidney dysfunction during follow-up.
Conclusion: These data uncover an important pathophysiological link between CKD and COPD. Patients with COPD and concomitant kidney injury are at high risk for progressive lung disease and adverse outcomes. Urinary DKK3 allows identification of COPD patients with progressive CKD, who might in particular benefit from preventive therapeutic strategies.

P022
 
Zwei multizentrische, randomisierte Phase-3-Studien mit intermittierendem oralen Roxadustat bei CKD Patienten mit Anämie unter Dialyse (PYRENEES) und ohne Dialysebehandlung (ALPS)
P023 

C. Esposito1, B. Csiky2, A. Tataradze3, M. Reusch4, C. Han5, W. Sulowicz6
1
ICS Maugeri SpA, Universität Pavia, Pavia, Italien; 2FMC Dialysezentrum, Pecs, Ungarn; 3Nationales Zentrum für Urologie, Tbilisi, Georgien; 4Astellas Pharma Europe B.V., Leiden, Niederlande; 5Astellas Pharma, Inc., Northbrook, IL USA; 6Dept. of Nephrology, Jagiellonen-Universität, Krakau, Polen

Hintergrund: Roxadustat ist ein oraler HIF-PHI in der Entwicklung zur Behandlung der renalen Anämie bei CKD Patienten.
Methode: In zwei europäische Phase III Studien wurden nicht-dialysepflichtige (NDD; ALPS) und dialysepflichtige (DD; PYRENEES) CKD-Patienten eingeschlossen.
In der doppelblinden ALPS-Studie wurden NDD-Patienten ohne Vorbehandlung mit ESAs und einem Hämoglobin (Hb) <10 g/dl 2:1 für die Behandlung mit Roxadustat oder Placebo über 52-104 Wochen doppelblind randomisiert.
In der offenen PYRENEES-Studie wurden DD-Patienten mit stabiler Hämo- oder Peritoneal-Dialyse mit einem Hb von 9,5-12 g/dl unter ESA-Therapie 1:1 für eine Roxadustat- oder ESA-Behandlung über 52-104 Wochen randomisiert.
Primärer Endpunkt war die Veränderung des durchschnittlichen Hb-Wertes in Woche 28-52 nach Behandlungsbeginn.
Sekundäre Endpunkte waren u. a. die Veränderung des durchschnittlichen LDL-Cholesterins in Woche 12-28 nach Behandlungsbeginn, Dauer bis zum Einsatz einer Rescue-Therapie (i.e. Bluttransfusion, ESA, i.v. Eisen (NDD-Studie) und durchschnittlicher monatlicher Verbrauch i.v. Eisen bis zur Behandlungswoche 36 (DD-Studie). Auftretende unerwünschte Ereignisse (UE) wurden ebenfalls ausgewertet.
Ergebnisse: In der NDD-Studie (ALPS) wurden 594 Patienten randomisiert (Roxadustat n=391; Placebo n=203) und in der DD-Studie (PYRENEES) 836 Patienten (Roxadustat n=415; ESA n=421).
Der durchschnittliche Anstieg des Hb in den Wochen 28-52 betrug 1,988 (0,953) für Roxadustat und 0,406 (0,979) für Placebo (p<0.001) bei NDD-Patienten sowie 0,396 (0,773) für Roxadustat und 0,183 (0,860) für ESA bei DD-Patienten (p<0.001).
Die durchschnittliche Veränderung (KI 95%) der LDL-Werte betrug -0,701 (-0,83; -0,57; p<0.001) mmol/l gegenüber Placebo (bei NDD-Patienten) und -0,377 (-0,451; -0,304; p<0.001) mmol/l gegenüber ESA (bei DD-Patienten).
Bei NDD-Patienten war Roxadustat gegenüber Placebo überlegen hinsichtlich der Zeit bis zum Einsatz einer Rescue-Therapie (HR [95% KI], 0,238 [0,17; 0.33]; p<0.001).
Bei DD-Patienten war Roxadustat gegenüber ESA überlegen hinsichtlich des monatlichen Bedarfs an i.v. Eisen (durchschnittliche Veränderung [95% KI], -31,9 [-41,4; -22,4]; p<0.001).
Häufige UEs in beiden Gruppen waren terminales Nierenversagen, Bluthochdruck, periphere Ödeme.
Zusammenfassung: Roxadustat erwies sich als wirksam bei der Erreichung und Erhaltung der Ziel-Hb-Werte gegenüber Placebo und ESA bei (NDD- und DD-) CKD-Patienten mit renaler Anämie.

Sponsor: Astellas Pharma Inc.

 
Are frequent stone removal procedures in patients with primary hyperoxaluria type III (PHIII) related to decline in kidney function?
P024 

C. Martin-Higueras, B. B. Beck, M. Zaniew, P. Sikora, B. Hoppe; La Laguna/E, Köln, Zielona Góra/PL, Lublin/PL, Bonn

Objective: PHIII is seen as the less problematic type of autosomal recessive inherited PH. This group of disorders in glyoxylate metabolism is clinically characterized by recurrent urolithiasis and/or progressive nephrocalcinosis, and, in type I and II, end-stage renal failure. The cause of PHIII was identified only in 2010 and unlike in PHI/II a remarkable low prevalence of symptomatic adults was observed, hence long-term clinical data are scarce. This phenomenon is commonly attributed to reduced penetrance of causative hydroxy-oxo-glutarate aldolase 1 gene (HOGA1) variants and a still unexplained tendency for clinical remission with age. Most PHIII patients present in early childhood with recurrent urolithiasis and undergo (repeated) stone removal procedures. We now hypothesized that repeated stone removal procedures may be associated with decline in kidney function.
Method: We retrospectively analyzed clinical and laboratory data of 41 genetically confirmed PHIII patients (0.5-29.3 years of age, with (20 different) biallelic mutations in the HOGA1 gene). Period of follow-up ranged from just diagnosed to 22 years.
Results: Recurrent urolithiasis was most prominently found in the first 3 years of life (>25% of patients). Not all patients experienced clinical remission, 3/6 patients > 20 years of age have ongoing kidney stone development. In addition, patients presented with nephrocalcinosis and/or urolithiasis. A high amount of stone removal procedures during the first years, but also later in life was observed. Urinary oxalate excretion is significantly elevated, and within the range of PHI/II. A decline in kidney function was observed, which is related to a decreased clearance of oxalate (figure). Two patients each post multiple stone removal procedures had CKD stages 2 or 3. Seven further patients had CKD stage 2, which was not related to stone removal.
Conclusion: PHIII is said to be the most favorable PH type, but early diagnosis is mandatory to treat the patients adequately and to avoid repeated stone removal procedures, which may have an influence on decline in kidney function. This decline may also be related to hyperoxaluria per se, as reported for PHI and II.

 
Rehabilitation bei Niereninsuffizienz
P025 

C. Grupp, T. Tümena, J. Trögner, W. Swoboda, K.-G. Gaßmann; Bamberg, Nürnberg, Marktheidenfeld, Erlangen

Hintergrund: Ältere Nierenkranke (NK) weisen, zunehmend mit dem Grad der Niereninsuffizienz, besonders häufig die Kriterien eines multimorbiden geriatrischen Patienten auf. Bei akuten Erkrankungen sind geriatrietypische Begleitphänomene wie Frailty für deren Verlauf und Prognose oft entscheidend. Bislang ist weitgehend unklar, ob Patienten mit eingeschränkter Nierenfunktion von rehabilitativen Maßnahmen sowohl in der Akutgeriatrie (AG) als auch stationären geriatrischen Rehabilitation (RG) in gleichem Maße wie Nierengesunde (NG) profitieren. Ziel war jetzt, diese Frage anhand der Auswertung einer großen geriatrischen Datenbank zu klären.
Methode: In der 2000 etablierten GiB-DAT-Datenbank der Arbeitsgemeinschaft für Geriatrie in Bayern (AFGiB) wird ein großer Teil der Be­handlungsfälle bayerischer geriatrischer Abteilungen anonymisiert gespeichert. In dieser Untersuchung wurden sämtliche Fälle der AG und RG der Jahre 2012-2019 ausgewertet. Folgende Parameter wurden evaluiert: Bei Aufnahme: Alter, Geschlecht, Kognition (Minimental Status Examination: MMSE), Emotion (Geriatric Depression Scale: GDS), Pflegegrad (PG); bei Entlassung: Anzahl der Diagnosen und Medikamente; bei Aufnahme und Entlassung: Selbsthilfefähigkeit (Barthel Index: BI), Mobilität (Timed up and go-Test: TUG), Wohnsituation (WS).
Ergebnisse: Sowohl in der AG als auch RG unterschieden sich NG (AG/RG n=116513/248831) und NK (AG/RG n=27294/45984) nicht relevant im Alter, Geschlecht, MMSE, GDS und PG. Leicht höher war bei NK im Vergleich zu NG die Anzahl der Diagnosen (AG: 10,7 vs. 9,3; RG 10,3 vs 8,3) und der Medikamente (AG 10,1 vs 9,3; RG 9,9 vs. 9,0). Keine wesentlichen Unterschiede zeigten sich zu Beginn der Rehabilitation bei BI, TUG und Wohnsituation. Der BI verbesserte sich bei NK/NG um +14,4/14,5 (AG) bzw. +21,1/21,9 (RG) Punkte, die Zahl der im TUG „gehfähigen“ Patienten um +22,1/20,6 (AG) bzw. 14,3/14,5% (RG). Die häusliche WS ließ sich bei 66,0/68,9 (AG) bzw. 81,6/81,5% (RG) erhalten. Eine Differenzierung nach dem Grad der Niereninsuffizienz (3-5/Dialyse) zeigte für keinen der Parameter relevante Unterschiede.
Zusammenfassung: Nierenkranke profitieren unabhängig vom Grad der Niereninsuffizienz in gleichem Maße wie Nierengesunde von rehabilitativen Maßnahmen in AG und RG im Hinblick auf eine Verbesserung von Selbsthilfefähigkeit und Mobilität sowie dem Erhalt ihrer Wohnsituation.

 
Detection of Changes in Renal Blood Flow Using Arterial Spin Labeling MRI
LA06 

Objective: Alteration in kidney perfusion is an early marker of renal damage. Magnetic resonance imaging (MRI) with arterial spin labeling (ASL) is a noninvasive promising approach to measure renal blood flow (RBF) without the use of contrast media. The purpose of this study consisting of three experiments was to evaluate if both acute and short-term changes in RBF could be detected using ASL-MRI technique.
Method: RBF as assessed by cortical (CRBF), medullary, and total renal blood flow (TRBF) were measured by ASL-MRI using FAIR True-FISP sequence. In the first experiment with 11 normotensive healthy individuals (NT) and 11 hypertensive patients (HT), RBF was measured at baseline and after both feet were covered with cold ice packs (cold pressor test) that activates the sympathetic nervous system. In the second experiment, RBF was measured in patients with chronic kidney disease (CKD) before and after a pharmacological intervention. In the third experiment, we compared RBF measurements between 3 different study populations (NT, HT, CKD individuals).
Results: Significant reduction in CRBF (p=0.042) and a trend in TRBF (p=0.053) were observed in response to the activation of the sympathetic nervous system. In the second experiment, a trend towards reduction of CRBF (p=0.051) and TRBF (p=0.059) has been detected after pharmacological intervention. In the third experiment, TRBF were significantly lower in patients with HT (309.5±17.3mL/100 g/min) and CKD patients (260.4±29.1mL/100 g/min) compared to NT individuals (338.7±30.0mL/100 g/min) (NT vs. HT-p=0.014, NT vs. CKD-p=0.004). TRBF was also lower in patients with CKD compared to HT (p=0.047).
Conclusion: Our data indicate that both acute and short-term changes in RBF could be detected using ASL-MRI. Moreover, we were able to detect differences in RBF between healthy and diseased individuals by needing only small sample size per group. Thus, ASL-MRI offers an advantage in conducting clinical trials compared to other technologies.

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