Continuous Renal Replacement Therapy in Acute Kidney Injury:

Pros and Cons

MD, PhD. Head of Extracorporeal Hemocorrection Unit, National Scientific Medical Research Center, Astana, Kazakhstan

Продленная заместительная почечная терапия при острой почечной недостаточности:

за и против

Dr Abduzhappar Gaipov

Acute Kidney Injury (AKI): definition

AKI is defined as any of the following:

• Increase in SCr by ≥0.3 mg/dl (≥ 26.5 µmol/l) within 48 hours; or

• Increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or

• Urine volume <0.5 ml/kg/h for 6 hours.

2012 KDIGO

AKI classification systems: RIFLE

Staging of AKI (KDIGO 2012)

Kidney International Supplements (2012) 2, 19–36

Conceptual model for AKI

Kidney International Supplements (2012) 2, 19–36

Evalution of current AKI

Increased frequency of adverse prognostic forms of AKI:

• Inhospital mortality increased ≥2 times, associated with sepsis, cardiopulmonary distress and multiple organ dysfunctions

• Increased group of “AKI on CKD“

• Increased frequency of non-oligouric AKI (50 - 70% of the AKI)

• Increased number of “catabolic” form of AKI

High mortality in the ICU

• Depending on definition of AKI, up to 50-60% of patients in the ICU

• Up to 70% of these will require RRT

• Independent risk factor for mortality, 50 - 60% mortality in critically ill

Curr Opin Nephrol Hypertens. 2007 Mar;16(2):64-70 Current Anaesthesia and Critical Care 2005; 16:321-329

AKI after cardiac surgery (n=813)

• According to the RIFLE criteria, 19.3% of patients had renal impairment after cardiac surgery.

• a 90-day mortality rate according to RIFLE:

Risk – 8,0%;

Injury – 21,4%;

Failure – 32,5%.

Kuitunen A et al. Ann Thorac Surg 2006; 81:542-546

AKI - treatment

• Treatment of AKI is principally supportive -- renal replacement therapy (RRT) indicated in patients with severe AKI.

• Goal: optimization of fluid & electrolyte balance

• Paranteral nutrition during the oligouria

• Multiple modalities of RRT:

– Intermittent hemodialysis (IHD),

– continuous renal replacement therapies (CRRTs)

– hybrid therapies, ie sustained low-efficiency dialysis (SLED)

Molecuar mechanisms of RRT

Water soluble molecules

“small”

“middle”

“large”

High Flux

Low Flux

Kuf <10 mL/h/mmHg

Kuf >20 mL/h/mmHg

30000-50000 Daltons

< 500 - 600 Daltons

Convection

Water soluble molecules Dialysers Mechanisms

Diffusion

Convection Diffusion Diffusion

Convection

Hemodialysis Hemofiltration Hemodiafiltration

Modalities of RRT

SCUF – Slow Continuous Ultrafiltration Медленная продолжительная ультрафильтрация

CVVH – Continuous Venovenous Hemofiltration Продолжительная вено-венозная гемофильтрация

CVVHDF – Continuous Venovenous Hemodiafiltration Продолжительная вено-венозная гемодиафильтрация

SLED – Slow low efficiency dialysis Медленный низкой эффективности диализ

EDD – Extended daily dialysis Длительный ежедневный диализ

IHD – Intermittent hemodialysis Интермиттируюший гемодиализ

IUF – Isolated ultrafiltration Изолированная ультрафильтрация

Intermittent

Continuous

Hybrid

Sürekli Venovenöz hemofiltrasyon (CVVH)

CVVH clearance (K) KHF = Qf x S Qf = Ultrafiltration rate S = Sieving coefficient S = Cef/Cb Cef = Concentration in Effluent Cb = Concentration in blood

Sürekli venovenöz Hemodiyafiltrasyon (CVVHDF)

CVVHDF clearance (K) KHDF = (Qf x S) + (Qd x Sd) Qf = Ultrafiltration rate S = Sieving coefficient S = Cef/Cb Cef = Concentration in Effluent Cb = Concentration in blood Qd = Dialysate rate Sd = Dialysate saturation

Pre-dilüsyon ve Post dilüsyon

Replasman sıvısı, filtreye girmeden verilir ise predilüsyon, filtreden sonra verilir ise postdilüsyon denilir

Devices for renal replacement therapy

CRRT machines Pump #

HD, UF

HD, UF, HDF-Online, SLED, EDD

CVVH: pre or post dilution

CVVH: pre , post and mixt dilution CVVHDF: pre or post dilution

CVVH: pre , post and mix dilution CVVHDF: pre, post and mixt dilution, Citrate protocole

iHD machines Pump # Possible modalities

Absolute and relative indications to initiate RRT in AKI

Gibney et al, Clin J Am Soc Nephrol 2008

CLINICAL PRACTICE GUIDELINES – AKI Initiation of RRT

UK Renal Association, 5th Edition, 2011

2012 KDIGO

CLINICAL PRACTICE GUIDELINES – AKI Which modality of RRT?

UK Renal Association, 5th Edition, 2011

2012 KDIGO

The choice of modalities of RRT

Optimal modality of renal replacement therapy in acute renal failure according to the clinical status of the patient. IIUF: intermittent isolated ultrafiltration; CEPD: continuous equilibrium peritoneal dialysis; TPE: therapeutic plasma exchange.

The choice of modalities of RRT in Septic patients

Comprehensive Clinical Nephrology: Fourth Edition

iHD vs CVVH: Kinetics of BUN in RRTs

Ronco C et al

Nephrol Dial Transplant 13[Suppl 6]:76-85

iHD vs CVVH:

Kinetics of HCO3 in RRTs

Ronco C et al

Nephrol Dial Transplant 13[Suppl 6]:76-85

iHD vsCVVH :

Effect on the hydration of brain tissue

Данные компьютерной томографии головного мозга

CRRT vs IHD

Prowle, J. R. & Bellomo, R. Nat. Rev. Nephrol. 6, 521–529 (2010)

Intermittent versus continuous renal replacement therapy for acute renal failure in adults

Copyright © 2008 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd.

15 RCTs with 1550 patients comparing CRRT with IRRT.

MEDLINE,

EMBASE,

Cochrane Central Register of Controlled Trials (CENTRAL)

У гемодинамически стабильных пациентов, вид заместительной почечной терапии не влиял на важные исходы лечения пациентов, и поэтому преимущество CRRT над IRRT у таких больных не обосновано по имеющимся данным. Пациенты, получившие лечения CRRT имели лучшие гемодинамикие параметры как СрАД.

PROS AND CONS OF DIFFERENT MODALITIES

COMPARE AND CONTRAST DIFFERENT MODALITIES

IHD SLEDD CRRT

Name Intermittent hemodialysis Slow (or sustained) low efficiency

daily dialysis Continuous renal replacement therapy

Mechanism and

molecules removed Dialysis – mostly low MWt

Small + middle molecules

with SLEDD/F Small + middle molecules with

CVVHDF

Use Ambulatory ESRD

Hyperkalemia

Critically ill

Hyperkalemia Critically ill

Non-ambulatory

Blood flow 300-400 mL/min 200-300 mL/min 100-200 mL/min

Dialysate flow 500-800 mL/min 1-2L/h 2-3 L/h

Efficiency High Moderate Low

Hemodynamic

stability Poor

(hypotension common) Good Good

Duration 3-4 h 3x/week 6-12 h daily Continuous (24h/filter)

Access Fistula or vascath

(must be good!) Fistula or vascath

(must be good!) Vascath only

Anticoagulation Not needed Usually not needed

(if filter clots lose 150 mL blood) Important

(if filter clots lose 150 mL blood) Dialysis

Dysequilibrium

Syndrome (DDS)

Insufficient time for equilibration between

compartments can cause cerebral edema N/A N/A

Drugs and

toxicology

Risk of rebound if high VD

Better for low VD (e.g. toxic alcohols)

Unclear effects on drug

pharmacokinetics Slower removal

Logistics Need tap water supply,

need hygienic effluent

removal, Technically difficult

High start up costs, low familiarity,

low running costs,

Hypophosphatemia

High workload, clearance limited by

interruptions, costly sterile dialysate

bags, immobility

Rev colomb anestesiol. 2013;41(2):88–96

Kidney International (2006) 70, 963–968.

Kitchlu et al. BMC Nephrology (2015) 16:127

Quality indicator of CRRT and measures

Indicators Measures

Dose prescription High vs. low dose

Dose delivery Percentage of prescribed dose delivered

Anticoagulation selection Heparin vs. citrate vs. none

Anticoagulation monitoring PTT monitoring, citrate monitoring

Anticoagulation complications Bleeding, hypocalcaemia, incidence of HIT

Treatment interruption Number of interruptions and duration of interruptions; time to establish new circuit

Catheter-related issues Infections, bleeding, obstruction/thrombosis

Circuit-related issues Filter clotting, pressure alarming

Rewa et al. Systematic Reviews (2015) 4:102

CRRT: What is new in 2015 ?

Stucker et al. Critical Care (2015) 19:91

J Crit Care. 2015 Jun 26.

Conclusion: A well-trained CRRT team could be beneficial for mortality improvement of AKI patients requiring CRRT.

CLINICAL PRACTICE GUIDELINES - AKI Treatment facilities & referral to renal services

• Guideline 5.1- Renal services should work together with other specialties to develop guidelines for the management of AKI. These should include clear guidelines with respect to when to request a renal referral. (1A)

• Guideline 5.2 – Specialist renal advice should be given with consultant renal physician input. (1B)

• Guideline 5.5 – Renal physicians and intensivists should work together to provide care for patients with AKI on the intensive care unit (ICU). Nephrology trainees should be trained to care for acutely ill patients with AKI. (2C)

UK Renal Association, 5th Edition, 2011

Thank you for attention