Supplementary Figure 1: Points of Sample Collection from CRRT Circuit

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1 Supplementary Figure : Points of Sample Collection from CRRT Circuit 5 3 Arrowheads indicate entry/exit points to the CRRT circuit. )Pre-filter sampling-port, ) predilution and anti-coagulant entry-port, 3) effluent sampling-port, ) post-filter samplingport and 5) post-dilution entry-port.

2 Supplementary Figure : Relationship between Dobutamine Dose and in Individual Patients Patient - Survived: Dobutamine and Dobutamine mcg/kg/min 3 Time Point Dobutamine Dobutamine mcg/kg/min Patient9 - Died: Dobutamine and Dobutamine. Time Point Dobutamine mcg/kg/min Patient5 - Died: Dobutamine and 5 5 Time Point Dobutamine Dobutamine mcg/kg/min Patient - Died: Dobutamine and Time Point Dobutamine

3 Supplementary Figure 3: Relationship Between RRI and. Scatter Plot of RRI and. RRI R=.9, p=.7

4 Supplementary Figure : Receiver-Operator Curve for SOFA as a Predictor of ICU Mortality ROC SOFA for ICU Mortality Sensitivity% 5 AUC=.73 p=. 5 % - Specificity%

5 Supplementary Figure 5: and Lactate Over Time for Individual Patients Patient : Survived - Haemorrhagic Patient : Survived - Sepsis and Hypovolaemia 5 Lactate Patient 3: Surivived - None Patient : Survived - None Patient 5: Survived - None Patient : Survived - Haemorrhagic Patient 7: Survived - Distributive and Cardiogenic Patient : Survived - None Patient 9: Died - Cardiogenic Patient : Survived - None

6 Patient : Survived - Cardiogenic Patient : Died - Septic Patient 3: Survived - Septic 5 Patient : Died - Septic Patient 5: Died - Cardiogenic Patient : Died - Septic Patient 7: Died - None Patient : Survived- None Patient 9: Survived - None Patient : Survived - Septic

7 Patient enrolment number, whether they died or survived their ICU-admission and the type of circulatory shock they had is indicated on each graph. is plotted on the left Y-axis on a logarithmic scale; lactate is plotted on the right Y-axis on a linear scale. The laboratory defined upper limit of normal for renin is demarcated with a red dotted line, while that of lactate is demarcated with a blue dotted line on each graph.

8 Supplementary Table : Patient Characteristics CRRT CKD Shock HT SOFA Meds. Survived Number of Patient Age Sex Admission Diagnosis AKI No. Stage * I-III # Samples ~ F Haemoperitoneum N N HH Y - Y 5 F Aspiration Pneumonia 3 N N S Y BB Y M Acute Renal Failure 3 N Y N N ARB Y F Mesenteric Art. Bypass N N N Y 5 - Y 5 73 F Post-CABG N N N Y 7 BB Y 55 F Liver Transplant 3 Y N HH N - Y 7 7 M Post Neo-Bladder 3 Y Y C+D Y 5 ACEi Y (7) 5 M SAH Fischer IV N N N N 7 - Y 9 M Post-CABG N N C N - N (7) M Polytrauma N N HH N BB Y 3 7 M Ao Valve Replacement N Y C N - Y 7 M Septic Shock 3 N N S N 7 - N 3 M Septic Shock N Y S N 5 ACEi, BB Y 5 57 F Septic Shock/Cirrhosis 3 Y Y S N - N M Cardiogenic Shock 3 Y N C N 5 - N M Septic Shock 3 Y N S Y 9 - N M PCP Pneumonia N N N Y ACEi N 3 F Post-Neurosurgery N N N N 3 - Y 9 5 M Polytrauma N N N N 5 - Y 7 79 M Urosepsis 3 N N S Y Spiro Y 7 Y=yes, N=No. * AKI stage was defined according to KDIGO guidelines. #CKD I-III was defined according to KDIGO guidelines. ~Figures in parenthesis in the Number of Samples column indicate the number of analyzable samples.

9 Supplementary Table : removal by continuous renal replacement therapy Patient No. Mode Qb (ml/min) Mass Inlet (µu/min) Mass Removal (µu/min) % Plasma Clearance Effluent Concentration (µu/min) % Removal by Membrane Adsorption HF.9 7. HDF 33 HDF HDF HDF HF=Hemofiltration; HDF = Hemodiafiltration; Qb = Blood flow. While removal was entirely by membrane adsorption for HDF, the minimal absolute values along with the exponential relationship between Qb and mass removal (Fig. ) indicate that renin has a low affinity for the AN9HF filter.

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