Aktuelle klinische Studien zum ANV
• Epidemiologie
• Prävention
• Konservatives Management
• Nierenersatztherapie
Agenda 10:20
• Epidemiologie
• Prävention
• Konservatives Management
• Nierenersatztherapie
Agenda 10:20
Natürlicher Verlauf des ANV
Cerda et al. Clin J Am Soc Nephrol 2008
16,968 critically ill patients with KDIGO
stage 2-3 AKI
Reversal of AKI was defined as alive and no longer meeting criteria
for even stage 1
Recovery was defined as reversal at hospital
discharge
Natürlicher Verlauf des ANV
Kellum et al. Am J Respir Crit Care Med 2016
Natürlicher Verlauf des ANV
Kellum et al. Am J Respir Crit Care Med 2016
Das AKD-CKD Kontinuum
Ferenbach & Bonventre. Nat Rev Nephrol 2015
Mortalität und CKD nach ANV
Sawhney et al. Br Med J Open 2015
Mortalität CKD
Parr & Siew. Adv Chron Kidney Dis 2016
Morbidität und CKD nach ANV
cohort study using data from Kaiser Permanente Northern California population: 43,611 adult patients hospitalized between 2008 and 2011 key exclusions:
– no documented blood pressure within 1 year prior to hospitalization – SBP >140 or DBP >90 within 1 year prior to hospitalization – prior diagnostic code for hypertension (x 2 or more) – no serum creatinine within 1 year prior to hospitalization – dialysis or transplant patients – no documented BP in 2 years after hospitalization
primary predictor: AKI (defined using KDIGO creatinine criteria) outcome: SBP >140 or DBP >90 during any ambulatory visit within 2
years after discharge
Bluthochdruck nach ANV
Hsu et al. J Am Soc Nephrol 2016
graded association between AKI severity and risk of elevated BP
Hsu et al. J Am Soc Nephrol 2016
Bluthochdruck nach ANV
cohort study using Department of Defense databases population: 3,846 critically injured US military personnel wounded in Iraq
or Afghanistan from 2002-2011, followed until 2013 key exclusions:
prior diagnosis of hypertension (only 84 out of 6000+) primary predictor: AKI defined using KDIGO creatinie criteria outcome: hypertension defined using ICD9 codes (401.x, 402.x)
if diagnosis assigned within first 90 days of injury, then a second diagnosis required after 90 days to confirm
results: adjusted HR 1.66 (1.28-2.14, P<0.001) for hypertension adjusted for demographics, Injury Severity Score (ISS), burn injury,
HR & MAP at time of injury HR for CKD 4.79 (2.53-9.08, P<0.001)
Stewart et al. Circulation 2015
Bluthochdruck nach ANV
• 10 studies with 90,251 patients • graded association between AKI severity and CHF risk (p=0.01
for interaction); limiting to studies that adjusted for baseline EF, association still holds
Odutayo et al. J Am Soc Nephrol 2017
Herzinsuffizienz nach ANV
HR 1.53 [95% CI: 1.50-1.57]
Re-Hospitalisierung nach ANV
• 111,778 matched pairs
• 18% re-hospitalized
• heart failure (13%)
• AKI (6%)
Silver et al. Am J Med 2016
Siew et al. J Am Soc Nephrol 2016
Risikofaktoren für rekurrentes ANV
1.3.1: Assess patients 3 months after AKI to evaluate the completeness of resolution, the detection of new-onset CKD or worsening of pre-existing CKD (1C)
Das AKD-CKD Kontinuum
• Epidemiologie
• Prävention
• Konservatives Management
• Nierenersatztherapie
Agenda 10:20
Statine und KM-induziertes ANV
Lee et al. PloS One 2014
Statine und OP-induziertes ANV
Lewicki et al. Cochrane Rev 2015
• 199 Patienten ohne Statin randomisiert zu: • 80 mg Atorvastatin 1 Tag vor dem Eingriff, 40 mg am
Morgen vor OP und danach 40 mg täglich (n=102),
oder
• Placebo (n = 97)
• 416 Patienten mit Statin randomisiert zu: • 80 mg Atorvastatin am Morgen der OP und danach
40 mg (n = 206), oder
• Placebo an beiden Tagen (n = 210)
Statine und OP-induziertes ANV
Billings et al. JAMA 2016
Statine und OP-induziertes ANV
Billings et al. JAMA 2016
200 Patienten ohne Statin randomisiert zu 80 mg Atorvastatin vor dem Eingriff, 40 mg am Morgen vor OP und danach 40 mg
Atorvastatin täglich, oder Placebo
Statine und OP-induziertes ANV
Park et al. Intensiv Care Med 2016
Remote Ischemic PreConditioning
• 240 Patienten mit hohem Risiko für ANV vor
herzchirurgischem Eingriff
• Aufpumpen einer Manschette am Oberarm auf
50 mmHg über individuellen systolischen Blutdruck
• 3 Zyklen über 10 Minuten direkt vor dem Eingriff: • 5 Minuten aufpumpen (Ischämie)
• 5 Minuten ablasen (Reperfusion)
Präkonditionierung und ANV
Zarbock et al. JAMA 2015
Präkonditionierung und ANV
Zarbock et al. JAMA 2015
Präkonditionierung und ANV
Meybohm et al. N Engl J Med 2015
Präkonditionierung und ANV
Meybohm et al. N Engl J Med 2015
Präkonditionierung und ANV
Gallagher et al. Kidney Int 2015
86 Patienten mit eGFR <60 ml/min/1,73m² vor Bypass-OP
Präkonditionierung und ANV
Gallagher et al. Kidney Int 2015
86 Patienten mit eGFR <60 ml/min/1,73m² vor Bypass-OP
Samstag 19.11.2016
High Impact Clinical Trials
Veighey K – Portsmouth (UK) Remote ischaemic preconditioning leads to sustained improvement in allograft function following live donor kidney transplantation
Veighey et al. ASN 2016
multi-centre multinational randomized controlled double blind clinical trial to determine if remote ischaemic preconditioning (RIPC) improves renal function after adult live donor kidney transplantation
2 x 2 factorial design – control
– early RIPC
– late RIPC
– dual RIPC
primary endpoint: iohexol GFR at 12 months
early RIPC placebo
late RIPC
dual 102
late alone 103
placebo early alone 102
placebo 99
Veighey et al. ASN 2016
High Impact Clinical Trials
3.08 (-0.89 to 7.04) Adjusted mean difference 1.19 (-2.77 to 5.15)
p value 0.128 0.555
n 159 172 166 165
55,9
58,3
56,8 57,6
50
51
52
53
54
55
56
57
58
59
60
Control Early Control Late
RIPC und eGFR nach 12 Monaten
Veighey et al. ASN 2016
eGFR
(ml/m
in/1
,73m
²)
• overall, eGFR difference between early RIPC and control:
4.82; 95% CI 1.60 to 8.03; p=0.003
• adjusted mean differences in
eGFR (ml/min/1.73m2) between
control & early RIPC groups:
1 year 3.77 (p=0.049)
2 years 3.94 (p=0.052)
3 years 5.16 (p=0.015)
4 years 5.55 (p=0.039)
5 years 5.05 (p=0.104) 30
40
50
60
eGFR
(ml/m
in/1
.73m
²)
3 12 24 36 48 60Time (months)
Mean +/- Standard Error:Control Late RIPCEarly RIPC
Veighey et al. ASN 2016
Early RIPC und eGFR nach 5 Jahren
30
40
50
60
eGFR
(ml/m
in/1
.73m
²)
3 12 24 36 48 60Time (months)
Mean +/- Standard Error:Control Late RIPC
• adjusted mean differences in
eGFR (ml/min/1.73m2) between
control & late RIPC groups:
1 year 1.03 (p=0.591)
2 years 1.42 (p=0.483)
3 years 1.86 (p=0.382)
4 years 5.89 (p=0.029)
5 years 2.00 (p=0.519)
• overall, eGFR difference between late RIPC and control:
1.62; 95% CI: -1.59 to 4.83; p=0.323
Veighey et al. ASN 2016
Late RIPC und eGFR nach 5 Jahren
30
40
50
60
eGFR
(ml/m
in/1
.73m
²)
3 12 24 36 48 60Time (months)
Mean +/- Standard Error:Control RIPC
• adjusted mean differences in eGFR
(ml/min/1.73m2) between control &
dual RIPC groups:
1 year 4.22 (p=0.058)
2 years 3.94 (p=0.096)
3 years 6.22 (p=0.012)
4 years 10.67 (p=0.001)
5 years 8.02 (p=0.027)
• overall, eGFR difference between RIPC and control:
4.21; 95% CI: 0.45 to 7.98; p=0.028
Veighey et al. ASN 2016
Dual RIPC und eGFR nach 5 Jahren
A
0%
2%
4%
6%
8%
Per
cent
with
gra
ft lo
ss
204 194 193 189 136 84Early RIPC 202 188 185 181 128 72Control
Number at risk
0 12 24 36 48 60Time (months)
Control Early RIPC
C
0%
2%
4%
6%
8%
Per
cent
with
gra
ft lo
ss
205 195 193 189 136 83Late RIPC 201 187 185 181 128 73Control
Number at risk
0 12 24 36 48 60Time (months)
Control Late RIPC
E
0%
2%
4%
6%
8%
Per
cent
with
gra
ft lo
ss
307 290 288 281 204 123Any RIPC 99 92 90 89 60 33Control
Number at risk
0 12 24 36 48 60Time (months)
Control Any RIPC
Veighey et al. ASN 2016
RIPC und Transplantatverlust
• 208 CKD Patienten (Serum-Kreatinin ≥1,7 mg/dl) • ACE-Hemmer bzw. AT1-Rezeptorblocker wurden mindestens 24 Stunden vor dem Herzkatheter in randomisierter Reihenfolge abgesetzt oder belassen
RAS-Hemmer und ANV
Bainey et al. Am Heart J 2015
RAS-Hemmer und ANV
Bainey et al. Am Heart J 2015
• Epidemiologie
• Prävention
• Konservatives Management
• Nierenersatztherapie
Agenda 10:20
Zielorientierte Therapie und ANV
Kellum et al. Am J Respir Crit Care Med 2016
Zielorientierte Therapie und ANV
Kellum et al. Am J Respir Crit Care Med 2016
EGDT – early goal-directed therapy (targeted fluids, vasoactive medication, and blood transfusions to central venous oxygen saturation (as a measure of oxygen delivery to the tissues) PSC – protocol-based standard care (simpler structured approach based on blood pressure and heart rate, and the clinical assessment by the study team)
Zielorientierte Therapie und ANV
Kellum et al. Am J Respir Crit Care Med 2016
early goal-directed therapy
protocol-based standard care
standard care
Kellum et al. Am J Respir Crit Care Med 2016
Zielorientierte Therapie und ANV
Kristalloide und ANV
Kristalloide und ANV
• double-blind, cluster-randomized, crossover design
• randomization occurred at the ICU level (n=2,278)
• frequency, dose, and rate of fluid prescription were at the
discretion of the treating clinician
• the primary end point was incidence of AKI
Young et al. JAMA 2015
Serum-Kreatinin Nierenersatztherapie
Young et al. JAMA 2015
Kristalloide und ANV
Kristalloide und ANV
Young et al. JAMA 2015
0.9% normal saline as the solution of choice
patients with alkalosis and hypochoremia (e.g. profound vomiting) patients with head injuries and brain edema
Buffered crystalloids as the solution of choice patients with evidence of sepsis patients with CKD patients requiring large amounts of fluid replacement
Kristalloide und ANV
Yunos. ASN 2016
Kristalloide und ANV
Plasma-Lyte 148® vs. Saline Study (PLUS) • ClinicalTrials.gov NCT02721654
• multi-centre, blinded, RCT
• estimated enrolment: 8,800 patients
• inclusion criteria includes fluid resuscitation of at least 500 ml or at least 5ml/kg
• patients who have previously received fluid resuscitation excluded
Balanced Solution vs. Saline in Intensive Care Study (BaSICS) • ClinicalTrials.gov NCT02721654
• multi-centre, blinded, RCT (2x2 factorial design)
• estimated enrolment: 11,000 patients
• Plasma-Lyte vs. saline; fast Infusion (999 mL/h) vs. slow Infusion (333 mL/h)
Agenda 10:20
• Epidemiologie
• Prävention
• Konservatives Management
• Nierenersatztherapie
Dialysebeginn bei ANV
Zarbock et al. JAMA 2015
231 kritisch kranke Patienten mit ANV und Plasma-NGAL
>150 ng/ml wurden randomisiert zu: • frühen Nierenersatztherapie
Beginn innerhalb 8 Stunden nach der Diagnose des ANV
ab KDIGO Stadium 2 (n = 112), oder
• späten/keiner Nierenersatztherapie
Beginn innerhalb 12 Stunden nach der Diagnose eines ANV im
KDIGO Stadium 3 (n = 119)
Dialysebeginn bei ANV
Zarbock et al. JAMA 2015
Dialysebeginn bei ANV
Zarbock et al. JAMA 2015
Dialysebeginn bei ANV
Gaudry et al. N Engl J Med 2016
Dialysebeginn bei ANV
Gaudry et al. N Engl J Med 2016
620 schwerstkranke beatmete Patienten mit ANV ab KDIGO Stadium 3 wurden randomisiert zu: • frühen Nierenersatztherapie Beginn sofort nach Randomisierung, oder • späten/keiner Nierenersatztherapie Beginn nur bei:
• schwerer Hyperkaliämie • schwerer metabolischer Azidose • Lungenödem • Serum-Harnstoff >112 mg/dl, oder • Oligurie länger als 72 Stunden nach Randomisierung
Dialysebeginn bei ANV
Gaudry et al. N Engl J Med 2016
Dialysebeginn bei ANV
Gaudry et al. N Engl J Med 2016
Donnerstag 17.11.2016
CKD and AKI Clinical Trials
Bridoux F – Paris (France) Treatment of myeloma cast nephropathy: a randomized study comparing high cut-off hemodialysis with standard hemodialysis Hutchison CA – Birmingham (UK) European trial of free light chain removal by extended haemodialysis in cast nephropathy: a randomised controlled trial
ASN 2016
MYRE study • 98 patients • bortezomib based
chemotherapy • intensive dialysis:
• 8 sessions (5 hrs.) over 10 days then thrice weekly
• HCO-HD vs. HF-HD • similar FLC levels at 3 months • dialysis independence:
• 43% vs. 33% (NS) at 3 months • 60% vs. 38% (p< 0.03) at 6
months
EuLITE trial • 90 patients • bortezomib based
chemotherapy • alternate day HCO-HD
• 2 filters in series • HF-HD at discretion of
nephrology • FLC levels similar at 3 weeks • dialysis independence:
• 52% vs. 56% (NS) at 3 months • 58% vs. 66% (NS) overall • no difference of eGFR at 2
years
HCO HD bei Myelom-Leichtketten
ASN 2016
0 2 4 6 8 10 12
0.0
0.2
0.4
0.6
0.8
1.0
Months
Cum
ulat
ive
inci
denc
e of
HD
inde
pend
ence
ControlHCO
Months
Sur
viva
l Pro
babi
lity
0 7 14 21 28 35 42 49 56 63 70
0.0
0.2
0.4
0.6
0.8
1.0
47 39 30 16 11 6 6 2 1 Arm=Control
46 42 31 22 15 10 7 5 2 Arm=HCO
Arm=Control Arm=HCO
MYRE study
Myeloma + proven MCN + hemodialysis requirement conventional high-flux dialyser vs. HCO Theralite
renal survival
p = 0.047
ASN 2016
Months
Survi
val P
roba
bility
0 6 12 18 24 30 36 42 48 54 60 66
0.00.2
0.40.6
0.81.0
48 41 35 22 15 11 7 6 4 1 1 Arm=Control
46 42 38 25 18 14 9 7 5 4 2 Arm=HCO
Arm=ControlArm=HCO
overall survival
p = 0.46
HCO – 56% HF – 52% p = NS
EuLITE trial
Renal function by 3 and 12 months
ASN 2016
HF – 66% HCO – 58% p = NS
3 months 12 months
total HCO-HD (43)
HF-HD (47)
0-3 months 68 40 28 infections 34 22 12* catheter related 9 5 4 lung 15 12 3 sepsis 4 2 2 others 6 3 3 non-infections 34 18 16
*p = 0.022
Serious adverse events
ASN 2016
EuLITE trial
Vielen Dank!
Agenda 10:20