Freitag, 02.10.2020

14:00 - 15:30

Poster DGfN 2020

Chronisches Nierenversagen 2 (P026 - P034; LA07)

 
Efficacy and safety of the long-acting C5 inhibitor ravulizumab in patients with postpartum atypical haemolytic uraemic syndrome
P026 

A. Gäckler, V. Dobronravov, G. La Manna, A. Denker, P. Liu, U. Schönermarck, M. Vinogradova, S.-S. Yoon, M. Praga; Essen, St. Petersburg/RUS, Bologna/I, Boston/USA, München, Moskau/RUS, Seoul/ROK, Madrid/E

Objective: Atypical haemolytic uraemic syndrome (aHUS) triggered by pregnancy is a rare and under-recognised disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor built on eculizumab, with a maintenance dosing interval of 8 weeks, is efficacious in treating aHUS. In this analysis, we report outcomes in a subgroup of patients with postpartum-aHUS enrolled in the 311 study.
Method: This was a global, phase 3, single-arm, multicentre trial evaluating the efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete thrombotic microangiopathy (TMA) response (simultaneous platelet count normalisation [≥150 x 109/L], lactate dehydrogenase [LDH] normalisation [≤246 U/L] and ≥25% improvement in serum creatinine at 2 separate assessments ≥28 days apart) through the 183-day initial evaluation period. Additional efficacy endpoints were: time to complete TMA response, haematological normalisation (platelet count and LDH), dialysis requirement status, and change in eGFR.
Results: Eight patients with postpartum-aHUS (mean age 36 [±8] years) were diagnosed within 12 days of delivery. Seven patients were white and one was Asian. Six patients (75%) had received plasma exchange/infusion before ravulizumab therapy; five (63%) were on dialysis. Complete TMA response was achieved in 7/8 patients (87.5%) in a median time of 32 days. Haematological normalisation was observed in all patients. By Day 29, all five patients on dialysis at baseline had discontinued dialysis, and by Day 183 all eight patients had improved CKD stage (defined based on eGFR value) by ≥1 category. Three possible treatment-related adverse events (non-serious) were noted in two patients (arthralgia and nasopharyngitis; urinary tract infection). All patients survived and no meningococcal infections occurred.
Conclusion: This is the first prospective analysis of a C5 inhibitor in postpartum-aHUS. Treatment with ravulizumab resulted in rapidly improved haematological and renal outcomes with no unexpected adverse events identified when administered at 8-weekly dosing intervals through intravenous infusion.
Figure: Median time to complete TMA response

P026


Disclosures:
Supported by Alexion Pharmaceuticals Inc. This is an encore abstract of the original published at ERA-EDTA congress 2020.

 
Osteopontin and its association with adverse events in the German Chronic Kidney Disease Study
P027 

I. Steinbrenner, Y. Cheng, F. K. Kotsis, J. Nadal, M. Schmid, M. P. Schneider, V. Krane, M. Nauck, K.-U. Eckardt, A. Köttgen, P. Sekula, U. T. Schultheiß; Freiburg, Bonn, Erlangen, Würzburg, Greifswald, Berlin

Objective: Osteopontin (OPN) is synthesized in the thick ascending limb of Henle’s loop and in the distal tubule and has been suggested to be an important factor in renal failure. Further studies are needed to fully understand its role in kidney (patho-)physiology and its potential as a marker of kidney disease progression and adverse renal events. We therefore evaluated the association of baseline OPN with a composite renal endpoint and all-cause mortality in a cohort of CKD patients, the German Chronic Kidney Disease (GCKD) study.
Method: OPN was measured from baseline serum samples using the Quantikine Human OPN Immunoassay. Coefficients of variation were <7%. Renal events included kidney failure treated with kidney replacement therapy (KRT: dialysis, transplantation), acute kidney injury, renal death, and all-cause mortality abstracted from hospital discharge letters and death certificates by trained physicians based on a standardized endpoint catalogue. Different linear regression models (dependent variables: eGFR, logUACR) adjusted for age, sex, center, HDL cholesterol, triglycerides, diuretic and RAS inhibitor medication intake, smoking, BMI, history of cardiovascular disease, diabetes mellitus, serum albumin, C-reactive protein, calcium, systolic blood pressure, and proteinuria as well as Cox proportional hazard models of time to a composite renal outcome (KRT+renal death) and mortality additionally adjusted for baseline eGFR were evaluated for serum log-transformed OPN.
Results: Over 6.5 years of follow-up, 480 KRT+renal death events and 570 deaths occurred among 4,950 GCKD patients. Mean age was 60.1 years (±12.0) with 60.3% men. Median OPN levels were 29.2 ng/mL (p25 20.7, p75 41.8). Cross-sectionally each unit of logOPN was associated with a 5.5 mL/min/1.73m2 lower eGFR on average (p<0.0001, 2.1e-31, 95% CI: -6.4 to -4.6) and a 1% change in OPN was associated with a 0.67% change in UACR (p<0.0001, 95% CI: 0.57 to 0.78). In prospective analyses, higher logOPN levels were associated with a higher risk of reaching the composite renal endpoint (adjusted hazard ratio [HR] 1.4, p<0.001, 95% CI 1.2-1.7). Adding AKI events (N=221) to the composite renal outcome did not change the results. Higher logOPN was also associated with a higher risk of all-cause mortality (adjusted HR 1.5, p<0.001, 95% CI 1.3-1.8).
Conclusion: Higher OPN levels in the GCKD study were associated with lower eGFR and higher UACR cross-sectionally, and with a higher risk of adverse kidney events and all-cause mortality, supporting OPN to be a potential marker of CKD progression and mortality.

 
Panta rhei – Diuretisch wirksame Pflanzen der Traditionellen Europäischen Medizin (TEM)
P028 

C. Bauer, J. Büntzel, M. Haubitz; Fulda, Göttingen

Hintergrund: Pflanzen, die zu einer Zunahme der Diurese führen, haben eine lange Anwendungsgeschichte in der Traditionellen Europäischen Medizin (TEM). Die klassische Indikation liegt in der „Durchspülungstherapie“ bei Harnwegsinfekten, Blasensteinen und Nierengrieß als Teeanwendung. Für die Mehrheit der Pflanzen ist jedoch nur eine aquaretische Wirkung beschrieben, nur wenige wirken darüber hinaus auch saluretisch. Eine systematische Zusammenstellung dieser Pflanzen fehlt bislang, ebenso eine Analyse der Studienlage.
Methode: 13 deutschsprachige TEM- und Phytotherapiebücher wurden auf Pflanzen mit einer harntreibenden Wirkung durchsucht. Hieraus wurde eine „Trefferliste“ erstellt. Für die Pflanzen, die in ≥50% der Bücher genannt wurden, führten wir eine systematische Literaturrecherche auf PubMed gemäß den PRISMA-Kriterien durch. Als MESH-Terms wurden die lateinischen Pflanzenbezeichnungen für die Suche verwendet. Eine zweite PubMed-Suche mit den MESH-Terms „herbal/medical plant“ und „diuretic/aquaretic/saluretic“ wurde parallel durchgeführt, um die Studienzahl zu erhöhen.
Ergebnisse: Die gescreente Literatur nennt insgesamt 106 Heilpflanzen, denen eine diuretische Wirkung zugeschrieben wird. Die am häufigsten genannten Pflanzen waren Wacholder (13 Treffer), Acker-Schachtelhalm und große bzw. kleine Brennnessel (jeweils 12 Treffer), Moor- und Hängebirke sowie Goldrute (jeweils 11 Treffer), Liebstöckel und Dornige Hauhechel (jeweils 10 Treffer), Löwenzahn (9 Treffer) und Kriech-Quecke (8 Treffer). Klinische Studien, die den Einsatz der Pflanzen am Patienten untersuchen, konnten für Birke, Schachtelhalm, Liebstöckel und Löwenzahn gefunden werden. Für alle Pflanzen gab es Hinweise auf eine diuretische Wirkung im präklinischen Tierversuch.
Zusammenfassung: Die Volksmedizin des deutschsprachigen Raumes kennt viele diuretische Pflanzen, von denen bisher jedoch nur ein Bruchteil in klinischen Studien auf ihre Wirkung untersucht wurde. Dabei ist dies erstrebenswert, da von den neun am häufigsten genannten Pflanzen fünf in den standardisierten Mischungen deutscher Blasen- und Harntees vorkommen und vermarktet werden.

 
One-year efficacy and safety of the long acting C5 inhibitor ravulizumab for the treatment of atypical haemolytic uraemic syndrome (aHUS) in adults
P029 

J. Menne, S. Cataland, M. Vallee, N. Heyne; Hannover, Columbus/USA, Boston/USA, Tübingen

Objective: Ravulizumab is a long-acting C5 inhibitor, derived from eculizumab, that is dosed q8w. Ravulizumab was approved in the US for patients with atypical haemolytic uraemic syndrome (aHUS) and is currently under evaluation in the EU based on the phase 3 trial (NCT02949128) efficacy and safety results at 26 weeks in patients with aHUS. Here, we report longer term results obtained from the trial during the ongoing extension period.
Method: This phase 3 trial was a single arm, global, open label study in adults (≥18 years of age) with aHUS naïve to complement-inhibitor therapy. Ravulizumab was administered i.v. q8w.
Patients that completed the 26-week initial evaluation period could enter the extension period. The primary endpoint was complete TMA response (normalisation of platelet count and LDH, and ≥ 25% improvement in SCr from baseline, measured at 2 separate assessments, at least 28 days apart). Secondary endpoints included haematological parameters , kidney function, and FACIT-fatigue scores. Treatment emergent AEs were evaluated. Here, interim cumulative data on primary and secondary endpoints through at least 52 weeks are reported.
Results: Forty-seven of 56 enrolled patients received at least one dose of ravulizumab in the extension period. The proportion of patients achieving the individual components of complete TMA response improved during the extension period (Figure). At last follow-up, the number of patients achieving complete TMA response increased from 30/56 (53.6%) in the initial evaluation period to 34/56 (60.7%). Of the 4 additional patients that reached complete TMA response, 3 had a previous kidney transplant and 1 initiated treatment one month after TMA presentation.
Although 3 new SAEs were reported during the extension period, there were no further fatal AEs. As in the primary analysis period, no meningococcal infections occurred through the last patient follow-up.
Conclusion: In the extension period of the Phase 3 trial, ravulizumab continued to have a good benefit: risk profile. The cumulative efficacy of ravulizumab to treat complement mediated TMA in patients with aHUS improved to 61% from 54% in the initial evaluation period. Most AEs occurred in the first 26 weeks, and there were no meningococcal infections identified in the study. These results suggest that with ravulizumab further improvement in efficacy is possible with longer treatment , no compromise in safety and better convenience of 8-week dosing intervals.
Figure: Complete TMA response and its components during initial 26 weeks and through all available follow-up data

P029


Disclosures
Supported by Alexion Pharmaceuticals Inc. This is an encore abstract of the original published at ERA-EDTA congress 2020.

 
DKK3 als neuer Biomarker zur Vorhersage der Krankheitsprogression bei Patienten mit ADPKD
P030 

M. Bartram, S. Arjune, S. Oehm, I. Becker, F. Grundmann, D. Fliser, R.-U. Müller; Köln, Homburg/Saar

Hintergrund: Die ADPKD ist die häufigste genetische Nierenerkrankung, welche im Erwachsenenalter zur Verlust der Nierenfunktion führt. Der variable Krankheitsverlauf macht die Identifikation der richtigen Patienten für gezielte Therapien notwendig. Aktuell steht hierfür vorrangig die MRT-basierte Volumetrie zur Verfügung. Einfach und quantitativ in Urin oder Blut bestimmbare Biomarker, welche eine Vorhersage des Nierenfunktionsverlustes erlauben, sind bislang in der Klinik nicht etabliert. Das im Nierentubulusepithel durch Stress sezernierte Glykoprotein Dickkopf 3 (DKK3) wurde kürzlich als Biomarker zur Abschätzung eines Verlustes der Nierenfunktion unterschiedlicher Genese beschrieben und nun bei ADPKD Patienten erstmals untersucht.
Methode: Bei 184 ADPKD Patienten aus dem AD(H)PKD-Register sowie 47 Kontrollen wurde DKK3 im Urin mittels ELISA bestimmt. Es erfolgte eine Korrelation der klinischen Daten aller Patienten, um so eine mögliche Rolle von DKK3 in der Stratifizierung von ADPKD Patienten zu untersuchen.
Ergebnisse: Bei den ADPKD Patienten zeigen sich im Vergleich zu den Kontrollen signifikant höhere DKK3 Werte (1970 ± 5287 vs. 112 ± 134,7 pg/mg Kreatinin). Es zeigte sich eine Steigerung der DKK3 Level mit Zunahme der Mayo Klasse (A/B 1262±2315 vs. D/E 3104±7627 pg/mg Kreatinin), als bestem etabliertem Biomarker der Progression bei ADPKD. Die Höhe des DKK3 Levels korreliert zudem mit der Nierenfunktion (eGFR). Die Ergebnisse bezüglich der eGFR sind interessant, da DKK3 nicht glomerulär filtriert wird und somit nach aktuellem Wissensstand unabhängig von der Nierenfunktion das Risiko einer Progression der zugrunde liegenden Nierenerkrankung vorhersagt. Passend zum akzelerierten klinischen Verlauf zeigen Patienten mit Mutationen in PKD1 höhere DKK3 Level im Vergleich zu PKD2 Patienten (PKD1:2304 ± 5119, PKD2:506,6 ± 526,8 pg/mg Kreatinin).
Zusammenfassung: DKK3 zeigt eine deutliche Korrelation mit der Nierenfunktion (eGFR) und der Mayo Klassifikation bei Patienten mit ADPKD. Dies könnte darauf hindeuten, dass DKK3 einen überproportionalen Nierenfunktionsverlust in diesem Kollektiv vorhersagt. Auch der zugrunde liegende Genotyp zeigt einen Zusammenhang mit den gemessenen DKK3 Level. Somit könnte DKK3 einen beschleunigten Krankheitsverlauf anzeigen. Weiterführende multivariante Analysen sollen nun untersuchen, ob die Bestimmung von DKK3 bei ADPKD Patienten eine bessere Stratifizierung in der Beratung als auch hinsichtlich therapeutischer Interventionen ermöglicht.

 
Biallelic variants of ROBO1 are associated with viable CAKUT phenotypes
P031 

M. Engesser, J. Münch, T. H. Lindner, J. Halbritter, B. Popp, S. Dateki, J. A. Hamm, A. T. Gülsen, C. Bergmann; Leipzig, Nagasaki/J, Knoxville/USA, Kartal/TR, Mainz

Objective: Congenital anomalies of the kidney and urinary tract (CAKUT) represent the most common cause of end stage renal disease (ESRD) in children. Despite emerging knowledge of disease causing gene variants, the majority of cases remain genetically unresolved. Genetic alterations in roundabout guidance receptor 1 (ROBO1), have been associated with neuronal and cardiac developmental defects in living individuals. ROBO1 is part of the SLIT2 signaling pathway that is pivotal for kidney development. However, a ROBO1-associated renal phenotype has only been described in a nonviable fetus so far (Rasmussen, Clinical Genetics, 2018).
Method: CKD-Gene Panel analysis of adults with undetermined ESRD, consecutive employment of GeneMatcher platform (Sobreira N et al., Hum Mutat. 2015 Jul 29), and literature research for identification of additional cases. Clinical workup of affected individuals and their relatives for deep retrospective phenotyping.
Results: We identified four patients (families), aged 2 to 44, from Germany, Japan, Turkey, and USA with biallelic likely pathogenic variants in ROBO1. Clinical manifestation consisted of vesical urethral reflux (n=2), posterior urethral valve (n=1), renal agenesis (n=1), genital malformation (n=1), and increased renal echogenicity (n=2). The only patient with follow-up to adulthood developed ESRD at age of 44. Further clinical characteristics were remarkably heterogeneous, including neurological developmental defects (n=3), intellectual impairment (n=2), strabism (n=3), and cardiac valve anomalies (n=1). Heterozygous relatives appeared to be unaffected.
Conclusion: To the best of our knowledge, this report is the first to describe life-born individuals with CAKUT due to likely pathogenic variants in ROBO1. Interestingly, renal involvement was only present if both alleles were affected. The expression of ROBO1 in multiple tissues could explain heterogeneous organ involvement. As the renal phenotype is variable, we suggest that further genetic modifiers, e.g. members of the SLIT2 signaling pathway, may contribute to disease severity. As a consequence, complete genetic analysis in CAKUT should comprise ROBO1 as a new recessive cause of disease. Conversely, in patients with already established ROBO1-associated cardiac or neuronal disease, screening for renal involvement is indicated.

 
Caspase-Funktionen bei Nierengesunden mit Hypertonus im Vergleich zu chronisch Nierenkranken
P032 

C. Ulrich, L. Kneser, S. Wildgrube, R. Fiedler, E. Seibert, J. Beckert, S. Fick, C. Schäfer, S. Markau, B. Trojanowicz, M. Girndt; Halle (Saale), Halle(Saale)

Hintergrund: Caspasen gehören zu der Familie der Endoproteasen. Sie erfüllen wichtige Aufgaben bei der Erhaltung der Homöostase durch Regulation von Inflammation und Zelltod. Während Caspase-1 und Caspase-4 funktionell den inflammatorischen Endoproteasen zuzuordnen sind, ist die Caspase-8 an apoptotischen Prozessen beteiligt. Kardiovaskuläre Erkrankungen werden maßgeblich durch entzündliche Prozesse beeinflusst. Hier wird untersucht, ob der Grad der Homöostasestörung in hypertensiven Nierengesunden (BP) beziehungsweise Nierenkranken (HD) unterschiedlich ist.
Methode: Zwanzig hypertone Dialysepatienten (HD: 57,7 ± 14,3 Jahre, 8 Frauen, 2 Diabetiker) sowie 20 gematchte Hypertoniker (BP: 58,0 ± 12,2 Jahre, 8 Frauen, 2 Diabetiker, GFR>90 ml/min/1,73 m²) wurden in die Studie eingeschlossen. Mononukleäre Zellen des peripheren Blutes wurden mittels Ficoll-Gradienten isoliert. Caspase-1 wurde durchflusszytometrisch (MFI), Caspase-4 mittels Kapillarelektrophorese (arbiträre Units) und Caspase-8 mittels ELISA-Technik (ng/ml) analysiert. Die mRNA-Isolation (Tempus-Tubes) und qPCR wurden mittels etablierten Protokollen durchgeführt.
Ergebnisse: Die CRP-Spiegel in beiden Kohorten waren nicht signifikant unterschiedlich. Die mRNA- Analysen ergaben einen signifikanten Anstieg der Caspase-8 Expression bei HD (HD: 2,9 ± 1,4 vs. BP: 2,3 ± 0,6; p<0,027), wohingegen die inflammatorische Caspasen -1 einen Trend zu höheren Expressionswerten bei BP zeigten (Caspase-1: HD: 1,4 ± 2,3 vs. BP: 1,9 ± 2,8; p<0,097). Die Caspase-4 mRNA- Expression war nicht unterschiedlich in beiden Gruppen. Auf Proteinebene waren sowohl Caspase-8 (HD: 0,06 ± 0,009 vs. BP: 0,06 ± 0,007; p<0,118) als auch Caspase-4 unverändert (HD: 1,3 ± 0,6 vs. BP: 0,9 ± 0,4; p<0,173). Lediglich die Caspase-1-Proteinexpression war signifikant bei BP-Patienten erhöht (HD: 12,6 ± 3,5 vs. BP: 16,0 ± 3,3; p<0,012).
Zusammenfassung: Die Daten deuten überraschenderweise darauf hin, dass inflammatorische Prozesse in Form einer Caspase-1 getriggerten Immunantwort die Zellhomöostase bei hypertensiven Nierengesunden im Vergleich zu den Nierenkranken stärker belasten. Die Beteiligung der Caspase-4 an diesen Prozessen scheint vernachlässigbar. Das Ausmaß der Caspase-8 gesteuerten Apoptose ist in beiden Kollektiven vergleichbar. Die Ursachen einer erhöhten Caspase-1- Aktivierung bei Bluthochdruck im Vergleich zu HD-Patienten müssen noch eruiert werden.

 
Estimation of LDL cholesterol in chronic kidney disease
P033 

F. Bauer, F. Seibert, B. Rohn, N. Babel, T. H. Westhoff; Herne

Objective: Most laboratories make use of the Friedewald formula to assess low-density lipoprotein cholesterol (LDL-C). The accuracy of this approach, however, crucially depends on triglyceride concentrations. Since hypertriglyceridemia is a characteristic trait of the lipid profile in chronic kidney disease (CKD), the present study examines the accuracy of the Friedewald formula in this population. It aims to derive and validate a more accurate equation for CKD.
Method: Cross-sectional study on two cohorts of subjects (overall n=3.514) with eGFR < 60 ml/min comparing directly measured LDL-C (LDL-Cmeas) as assessed by an enzymatic assay (Roche, Switzerland) to concentrations estimated by the Friedewald (LDL-CF) and the Martin's formula (LDL-CM). Accuracy was analyzed by Bland-Altmann and linear regression analyses. In the first cohort a novel formula was derived to assess LDL-C in CKD. The formula was validated in cohort 2.
Results: Cohort 1 comprised 1738 subjects, cohort 2 1776 subjects. Mean eGFR was 29.4±14.4 ml/min. In cohort 1 LDL-CF was highly correlated with LDL-Cmeas (R2 0.92), but significantly underestimated LDLmeas by 11 mg/dl. LDL-C=Cholesterol-HDL-triglycerides/7.98 was derived as the optimal equation for the calculation of LDL-C in cohort 1 and was successfully validated in cohort 2 (bias of 1.6 mg/dl). The novel formula had a higher accuracy than both the Friedewald (bias -12.2 mg/dl) and the Martin's formula (bias-4.8 mg/dl).
Conclusion: The Friedewald formula yields lower LDL-C concentrations in CKD than direct enzymatic measurements, which may lead to undersupply of this cardiovascular high risk population in a treat-to-target approach.

P033-1
P033-2
 
Evaluation of risk factors for adverse events and mortality in adult HD patients with atrial fibrillation: long-term cohort study on German network data
P034 

K.-A. Brensing, A. Ochsmann, H. Reichel, G. Lonnemann, H. Omran, J. Duttlinger; Bonn, Villingen-Schwenningen, Langenhagen, Düsseldorf

Objective: HD patients with atrial fibrillation (AF) are at high risk for cardio-vascular events, bleeding and rapid vascular/valvular calcification. Thus, vitamin-K based oral anticoagulation (VK-OAC) is under debate, since prospective trials are missing and register studies mostly use larger US data. We evaluated long-term outcome in a large German HD-cohort.
Method: We used pseudonymized benchmarking data (2013-2018) of 16226 adult chronic HD patients (informed consent) from DNeV dialysis network. Diagnoses were coded by “International Classification of Diseases (ICD)” and drugs via “Anatomical Therapeutical Chemical (ATC)” codes. Risk scores (Carlson Comorbidity Index=CCI, CHA2DS2-VASc and HAS-BLED) were tested for de-novo outcome prediction.
Results: At baseline, 2812 (17,3%) HD-patients had coded AF. CHA2DS2-VASc (4.0/SD1.5) and HAS-BLED (3.2/0.9) indicated high risk for embolism/bleeding. Apart from dialysis-related heparin-supply four main approaches were identified: No therapy, VK-OAC, Heparin or only Aspirin/Clopidogrel (Asp/Clop). Baseline event risk scores were not related to events (overall 9.3%) and similar for all four regimes, especially for cerebral adverse events (3.8%; R: 3.9-4.4%). VK-OAC had higher bleeding rates (6.4%; p<0.001) compared to Asp/Clop (3.5%) or no therapy (4.2%).
Overall 6-yr mortality was high (63%; Kaplan Meier median survival 2.9 yrs). In patients with unaltered therapy (n=1834; 65%) VK-OAC and Asp/Clop had similar mortality (2.8 vs. 2.9 yrs median survival; NS), both were superior to heparin or no therapy (1.6 or 1.8 yrs median survival; p<0.001). Also similar survival for elderly (>75 yrs: 2.3 yrs; both), higher CCI (>6: 2.3 vs. 2.5 yrs; NS) or both (>75 yrs+CCI>6: 2.0 vs. 2.2 yrs; NS). Cox-Regression (multivariate) showed only VK-OAC, Asp/Clop, serum albumin, age and CCI  as related to mortality (p<0.001).
Conclusion: De-novo thromboembolic events were low (<0.9%/yr) and similar for active and no active therapy, suggesting major beneficial impact of regular dialysis-related heparin-supply. Since VK-OAC had more bleeding but no survival benefit future trials should compare drugs and/or new interventional approachs (i.e. left atrial appendage occluder) with Asp/Clop as standard control. So far, treatment of AF in HD patients should avoid VK-OAC and prefer Asp/Clop as current best first choice therapy in Europe, where DOACs are unlabeled for ESRD. Age and comorbidity should be considered for start/stop of antithrombotic therapies rather than non-predictive CHA2DS2-VASc and HAS-BLED scores.

 
Accuracy of assessing change of renal function by estimated glomerular filtration rate
LA07 

J. Kolwelter, K. Striepe, A. Bosch, D. Kannenkeril, C. Ott, M. Schiffer, R. E. Schmieder; Erlangen

Objective: Detection of hyper-/hypofiltration in the early stage of chronic kidney disease (CKD) prior to any apparent organ damage is important to intercept and prevent progression of CKD. Clinicians rely on the glomerular clearance calculated by estimating equations based on serum creatinine, age, sex, ethnicity and body size. Our study analysed whether the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation compared to the inulin clearance, considered to be the gold standard, is able to detect short-term changes in renal function.
Method: In our retrospective, single-center, observational study, 190 patients who participated in placebo-controlled, clinical trials between 2005 and 2013 were included. In each patient, we measured, at baseline and follow-up visit, with the same methodology the glomerular filtration rate (mGFR) by applying constant infusion input clearance technique with inulin. Simultaneously, serum creatinine was assessed and estimated glomerular filtration rate (eGFR) calculated by CKD-EPI equation. Follow-up parameters were analysed after short-term pharmacological intervention (4, 9 and 12 weeks respectively).
Results: A total of 190 patients, aged 59±9 years and including 135 (71%) males, were analysed. At baseline, average mGFR was 111±20ml/min/1.73m², whereas eGFR was lower with 93±13ml/min/1.73m². An almost curvilinear relationship between the ratio of eGFR and mGFR in relation to mGFR shows an underestimation of mGFR in the upper normal range. After a short-term pharmacological intervention, average mGFR change was -1.65±14ml/min/1.73m² and average eGFR change was -2.35±6.6ml/min/1.73m². For a mGFR of 111ml/min/1.73m², a change of mGFR by ±10% equals ±11ml/min/1.73m² and corresponds to an eGFR range of 25ml/min/1.73m². For example, a mGFR change of -11ml/min/1.73m² corresponds to an eGFR change of -3.5ml/min/1.73m² (95% CI from -16.3 to 9ml/min/1.73m²) and an mGFR change of +11ml/min/1.73m² corresponds to an eGFR change of -0.5ml/min/1.73m² (95% CI from -13 to 12ml/min/1.73m²). Furthermore, the Blant Altman plot shows wide limits of agreement ranging from -25 to 27ml/min/1.73m² with many points lying far from the mean line, also indicating poor agreement between mGFR and eGFR change.

LA07


Conclusion: In our analysis, the agreement between eGFR by CKD-EPI and mGFR was at best modest. The CKD-EPI equation may be sufficiently accurate to be used as medical tool, but is not precisely enough to detect short-term change in renal function.

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