Acute Kidney Injury (AKI)KDIGO Clinical Practice Guidelines

Ali AlSahow

Introduction

Common & serious medical emergency characterized by:

1) Rapid decline in GFR that evolves over hrs-days-wks

2) Retention of waste products & dysregulation of ECV & electrolyte

3) Oliguria with U/O 0.5 ml/min/d complicates 50% of cases

4) High mortality rate with high rate of development or progression of CKD

1802 – W. Heberden: Gives the 1st description of AKI as Ischria Renalis – Renal Retention

1909 – W. Osler: Describes AKI as acute Bright illness in Principles & Practices of Medicine

1917 – F. Davies: Describes AKI as war nephritis in WW1 in the Lancet

1941 – Waters & Beall: AKI D/T crush injuries during 1941 London bombing in WW2 explained

1945 – W. Kolff: 1st successful hemodialysis for AKI in Holland at the end of WW2

1951 – H. Smith: Coins term ARF in The Kidney: Structure & Function in Health & Disease

2004 – ADQI: Coins the term AKI as the official scientific term

Historical Background of AKI

Definition & Staging of AKIStage Cr criteria UO criteria

1

Increase in Cr by ≥26.5 µmol/l within 48hrsOR

50 – 99% increase in Cr from baseline Baseline is known or presumed to have

occurred within prior 7 days

< 0.5 ml/kg/h for 6-12h

2 100 – 199% rise in Cr < 0.5 ml/kg/h for ≥ 12h

3

≥ 200% rise in CrOR

Cr rising ≥ 354 OR

Initiation of RRT

In pts younger than 18 decrease in eGFR to < 35 ml/min/ 1.73 m2

< 0.3 ml/kg/h for ≥ 24h

OR Anuria for ≥ 12h

Lack of standardized definition made incidence / outcome unclear Incidence is rising & will continue to rise Population is ageing with multiple comorbidities & polypharmacy

A. Developed countries: AKI affects 20% of adults & 35% of children hospitalized for acute illness AKI affects 65% of ICU pts & 5-10%% of all ICU pts will require RRT Subacute kidney injury affects 1% of hospitalized pts & raises mortality

Rise in Cr over more than 7 days

B. Developing Countries: Information come from small studies with low methodological quality Incidence is high & rising with high morbidity / mortality rates & cost

Socioeconomic & environmental factors influence rate / etiology / outcome Infectious diseases, obstetric complications, envenoming (snake/spider bites)

Epidemiology of AKI

Pattern of AKI & Country Income High & Most Middle Income Countries:

Well developed health care systems & optimal renal services

1) Occurs mainly in ICU

2) Associated with MOF

3) D/T sepsis, trauma or surgery

4) Affects mainly the elderly

5) Difficult to prevent

6) Expensive to treatLow & Some Middle Income Countries: Poorly developed health care system & poor renal services

1) Seen in Various hospitals (1o, 2o, 3o) & various hospital units

2) MOF less common

3) D/T infections or diarrhea

4) Affects Mainly young otherwise healthier subjects

5) Preventable

6) Inexpensive to treat if detected early but too costly for pt if detected late

Mortality for hospitalized AKI pts is 3-5 X higher than non-AKI pts Estimated AKI associated mortality: 24% for adults & 14% for

children In hospital mortality is 25% W/O RRT & 60% with RRT

90 day AKI mortality is 35% W/O RRT & 45% with RRT

90% of cases with MODS

AKI – associated mortality is decreasing in rich countries Despite ageing population, more comorbidities & more illness

severity

Avoidable deaths in poor communities are still unacceptably high

Up to 50% of AKI survivors are left with CKD or ESKD 15-30% of RRT requiring AKI pts remain RRT dependent at discharge

Number drops at 6 & at 12 months

Risk factors for lack of recovery Old age, Severity of CKD at baseline, Severity of AKI & Fluid overload

Outcome of AKI

Functional Pre-Renal injury or stress D/T hypoperfusion: The most common cause of AKI responsible for 50-60% of cases

70% of community-acquired & 40% of hospital-acquired Severe hypoperfusion is the commonest cause of ischemic ATN

Structural Renal injury: Intrinsic AKI accounts for 40% of all cases

Ischemic/Toxic tubular injury (ATN) causes 90% of such cases Interstitial injury causes 10% of cases Glomerular/Microvascular disease causes 5% of cases Macrovascular injury is uncommon

Obstructive Post-Renal injury: Acute obstruction causes <5% of cases of AKI

It has to be bilateral or unilateral with solitary kidney

Etiology of AKI

Complications of AKI

1) Hyperkalemia with risk of malignant arrhythmias

2) Metabolic Acidosis decreasing CO & gut barrier function

3) Hyperphosphatemia & Hypocalcemia

4) Volume overload causing Pulmonary edema & Hypertension

5) Delayed wound healing

6) Anemia

7) Bleeding tendency D/T plt dysfunction

8) Increased risk of infections D/T WBC dysfunction

9) Encephalopathy / Pericarditis / Tamponade

10) Stress GI ulcers

11) Compromised investigations by contraindicated contrast

12) Compromised management by contraindicated drugs

ISN 5 R’s Approach to AKI Management

1. Risk Assessment: Assess risk factors for development, & progression of AKI Prevent exposure to insults in high risk pts Use Scoring Systems / Screening / Electronic Surveillance Systems

Electronic surveillance for drug dose modification / Avoidance

Risk Factors for AKIA. Non-modifiable:1) Old age

2) Male sex

3) Black race

4) Comorbidities:

a) Pre-Existing CKD

b) DM

c) HTN

d) CLD / IBD

e) CHF / CAD / Recent MI

f) PAD

g) COPD

h) Malignancy

B. Potentially modifiable:1) Anemia / Hypoxemia

2) Sepsis

3) Trauma

4) Contrast / Nephrotoxic drugs

5)Volume status

a) Volume Depletion

b) Volume Overload

c) Using colloids / Cl rich fluids

6) Surgery:

a) Cardiac surgery

b) Major non-cardiac surgery

c) Emergency procedures

C. Environmental Factors:1) Poor Sanitation & No clean water

2) Poor control of parasites & vectors

D. Infrastructural Factors:1) Poor HC budget & Services

2) Poor Transportation

High & Most Middle Income Countries:1) Sepsis

2) Circulatory shock

3) Trauma & Burns

4) Cardiac Surgery & Major non – cardiac Surgeries

5) Nephrotoxic Drugs & Agents

Low & Some Midle Income Countries:1) Diarrhea

2) Obstetric Complications Including septic abortion

3) Infections: Malaria, Leptospirosis, Dengue Fever, Cholera

4) Animal Venoms: Snakes, Wasps, Spiders

5) Natural medicines & Natural dyes

6) Prolonged Heavy Physical Work in Unhealthy Environment

Exposure to be avoided in high risk pts

ISN 5 R’s Approach to AKI Management

2. Recognition of Injury: Diagnose & Stage AKI early according to Cr & U/O criteria Electronic alert system to alert about rise in Cr or drop in U/O Telemedicine & point of care testing Novel biomarkers?

They must produce real outcome improvement & cost effectiveness

ISN 5 R’s Approach to AKI Management

3. Response to Injury: The ABC’s Of Non-Dialytic Management of AKI

Correct reversible factors Avoid further exposure to insults - Nephrotoxins Manage complications – Volume overload, Acidosis, Hyperkalemia

1) Identify the cause of AKI & start specific therapy

2) Judge volume status: BP, HR, JVP, Postural BP, Skin turgor, U:Cr Fluids &/or inotropes to optimize CO, BP & renal perfusion if dry & ↓BP Diuretics to optimize urine output for volume overloaded pt

3) Correction of K / HCO3 / Ca / PO4 / Uric acid disorders

Use NaHCO3 cautiously to avoid volume overload & hypernatremia

4) Adequate BS control to keep BS 6.1-8.3 lowers mortality

5) Search for & aggressively treat infections with antibiotics

6) ESA for anemia

7) Early enteral nutritional support better than parenteral nutrition AKI is a pro-inflammatory state with protein hypercatabolism Protein intake is 1g/kg/d for non-catabolic non-dialyzed pts Protein intake is 1.5g/kg/d for IHD & 1.7/kg/d for CRRT & catabolic pts Total energy intake of 20-30 Kca/kg/d is advised for any stage of AKI

8) Adjust doses of drugs that are renally excreted or protein-bound

9) Avoid nephrotoxins: Dye, aminoglycosides, ampho B, NSAIDs

10) Assess the need for urgent RRT

Hemodynamic Support - Fluids In absence of hemorrhagic shock use crystalloids rather than colloids as

initial management for volume expansion in pts with AKI or at risk of AKI

No conclusive evidence that colloids are safer or more effective Colloids may be better for SBP in CLD or when large volume needed

Cost of colloids is higher

Hypertonic starch may be nephrotoxic – Osmotic Nephrosis Not yet proved that LMW colloids (iso-oncotic) less nephrotoxic

Balanced crystalloids (RL & Hartmann) less Cl & less osmolality than NS Less Acidosis, Less ↑K, Less Coagulopathy, Better pt & renal outcome

Maintenance fluid requirement per day:

25-30 ml/kg/ d H2O + 1 mmol/kg/d Na/K/Cl + 50-100 g/d glucose

This does not take into account ongoing losses / oliguria / hyperkalemia

Aggressive fluid repletion in the early setting is probably beneficial

Restrictive fluid approach better once AKI occur & hemodynamics stable

Positive fluid balance increases AKI mortality

Hemodynamic Support - Vasopressors

Use vasopressors plus fluids in pts with vasomotor shock High CO – Low SVR in septic shock, pancreatitis, burns & CLD

Persistent hypotension despite optimization of IV volume status

Vasopressors needed to preserve or improve renal perfusion

Not known which vasopressor most effective for prevention or treatment of AKI & septic shock NA is useful for MOF or sepsis

Vasopressin may be used for shock refractory to NA Improves BP & enhances diuresis

May reduce progression of AKI & lowers mortality in septic shock

Dopamine may be more arrhythmogenic compared to NA

Protocolized Hemodynamic Management

Protocol – based management of hemodynamic & oxygenation Prevent development or worsening of AKI in septic shock or high

risk postoperative pts

Early Goal – Directed Therapy (EGDT) Early detection & management of hypotension

Fluids, blood products, O2 delivery optimization, vasopressors use

Reestablish tissue perfusion within 6hrs aiming for:

1) Return of MAP to ≥ 65 mmHg

2) CVP between 8-12 mmHg

3) Improvement in blood lactate level

4) Central Vein Oxygenation Saturation > 70%

5) UO ≥ 0.5 ml/kg/hr

EGD septic shock resuscitation had no impact on outcome - NEJM

Diuretics in AKI Loop diuretics inhibit Na-K-2Cl cotransporter in TAL of LoH

No evidence they reduce incidence or severity of AKI or mortality

Minimal human data to support the following benefits:

1) Reduced ATPase activity & renal tubular O2 consumption may

decrease ischemic damage of vulnerable outer medullary tubules

2) Increased UO may wash out necrotic debris blocking tubules

3) Inhibition of PG dehydrogenase reduces renovascular resistance & may increase renal blood flow

May cause interstitial nephritis & thrombocytopenia High dose may cause ototoxicity

Do not use diuretics to prevent or treat AKI They do not influence recovery from AKI or mortality

Use diuretics to manage volume overload & hyperkalemia

Adjust dose according to renal function

Dopamine – Receptor Agonists1) Dopamine: Low-dose dopamine IVI in healthy ppl causes renal vasodilation

This increases GFR & induces natriuresis Dopamine increases renal vascular resistance in AKI pts Dopamine has no value in prevention or treatment of AKI May cause tachyarrhythmias & Cardiac & GI ischemia

2) Fenoldopam Dopamine receptor 1 agonist W/O systemic α or β stimulation

24h IVI may prevent AKI in high risk cardiac surgery Continuous IVI in ICU for septic shock may lower rate of AKI Early continuous IVI may help in treatment of AKI in critically ill pts Ineffective for prevention of CI – AKI Guidelines do not suggest its use yet, waiting for more evidence

1) AKI in renal transplant pt

2) AKI complications

3) AKI stage 3

4) AKI on CKD stages 3/4

5) Resolved AKI with residual impaired GFR, HTN or Proteinuria

6) AKI of unknown etiology

7) AKI not responding to therapy Remember:

Density of physicians in many African countries is 0.02-0.3/1000 WHO recommend 2.3 professionals per 1000 population Nephrologists cannot handle all cases everywhere

Shrinking number of nephrologists & increasing demand Involve PC, ED & IM physicians & nurses

Referral to Nephrologist

ISN 5 R’s Approach to AKI Management

4. Renal Replacement Therapy in AKI: Timing of Initiation, Modality, Dose & Duration of RRT

Timing of RRT in AKIUrgent Indications

1) Severe K not responding to therapy

2) Severe acidosis (pH <7.1) not fixed by NaHCO3 used for volume restoration

3) Uremic Encephalopathy

4) Uremic Pericarditis

5) Severe pulmonary edema not responding to diuresis

6) Relative indication: Cr > 500 & / or Ur > 50

Non – Renal Indications for RRT: Dialyzable toxins such as barbiturates, methanol, theophylline Severe hyperthermia Severe inflammatory response in septic unstable pt W/O severe AKI?

Timing of RRT in the absence of urgency is not clear

Early initiation does not improve pt’s survival or renal recovery

RRT induced hypotension & arrhythmias may delay recovery

Vascular access has complications

RRT requires anticoagulation

Do not delay RRT unnecessarily when benefit outweighs risks

Do not use diuretics to enhance renal recovery or reduce RRT dose

Consider likelihood of renal recovery, degree of dysfunction in other organs, need for fluid intake (nutrition, drugs, blood)

Timing of RRT in AKINon – Urgent Indications

RRT Modality for AKI

Outcome similar in critically ill AKI pts treated with CRRT & IHD

Mortality, Renal recovery & Length of hospitalization

CRRT is preferred for hemodynamically unstable pts

SLED may be better than IHD for unstable pts

CRRT is preferred with acute brain injury or brain edema

IHD – induced hypotension may compromise cerebral perfusion

Fluid shift from rapid solute removal may induce disequilibrium

Conventional Intermittent HDAdvantages

1) Cheap & low work load

2) Small amount of anticoagulation required

3) Intermittent nature allows diagnostic & therapeutic procedures 3-4 sessions per wk & 3-4 hrs per session

4) Adequate removal of excess fluid by UF

5) Clearance mainly by diffusion which is excellent for small solute Excellent for severe hyperkalemia & severe acidosis

Clearance can be enhanced by:

Increasing dialysis duration & frequency

Increasing Qb (above 200-300ml/min) & Qd (above 500-800ml/min)

Using large (high efficiency) & porous (high flux) membrane

Skilled personnel required

Difficult fluid control with intermittent therapy

Rapid solute shift can cause cerebral edema

Avoid in head trauma, hepatic encephalopathy, brain edema, ↑ICP

Not recommended in hemodynamically unstable pts

Tolerance in critically ill unstable pt is improved by:

Cooling dialysate to cool core To to improve SVR & venous tone

Increasing time & frequency to slow down fluid & solute removal

Na profiling & UF profiling

Conventional Intermittent HDDisadvantages

CRRTAdvantages

Simple for ICU nurses to operate

Assures Hemodynamic stability in critically ill pts D/T:

Gentle fluid & solute removal W/O fluctuations

Improves gas exchange, fluid balance & biochemistry

Allows aggressive & early enteral / parenteral nutrition

Reduces risk of brain edema especially in pts with CLD

To loss by dialysis circuit reduces core To improves SVR/venous tone

Clearance = IHD with UF rate of 35ml/Kg/h (2L/h in 70 Kg pt) / 24h

? Avoiding episodes of hypotension may enhance renal recovery

? Filtration/adsorption of inflammatory cytokines/cardiac depressants

CRRTDisadvantages

1. Expensive with use large amounts of substitution fluids

2. High work load with 24h operation

3. Requires heavy anticoagulation

4. Pt immobilization

5. Downtime may cause loss of expensive disposables

6. Loss of nutrients, vitamins & trace elements

7. Different drug clearance & dosing & affected by downtime

8. Hypothermia?

9. ? Removal of useful anti-inflammatory molecules

Alternative Modalities1) Extended Daily Dialysis (EDD):

Good IHD clearance plus gentle CRRT fluid & solute removalConventional dialysis machine with Qb 200ml/min & Qd

300ml/minRuns for long periods (6-12hr/d) allowing investigations /

proceduresLess anticoagulation & faster correction of acidosis than

CRRT

2) Pulse high volume (HV) CVVHF: CRRT for AKI in septic pts with MODS

Removes middle & large MW inflammatory mediatorsUF rate of 85ml/kg/hr for 6-8hrsFollowed or preceded by UF rate of 35ml/kg/hr

3) Slow Continuous Ultrafiltration (SCUF): No dialysate or replacement fluid is needed as no HD or HF Safe & effective removal of fluid of up to 2L/hr

Dose of RRT in AKI

RRT dose should be prescribed before starting each session Assess actual delivered dose to adjust the prescription Delivered dose is frequently less than prescribed

Hemodynamic instability, access or filter problems, down time Dose improved by more time, bigger filter, higher QB & QD & UFR

Recommended Kt/V is 3.9 / wk for IHD or SLED Recommended effluent volume is 20-25 ml/kg/h for CRRT – 42L/d

Peritoneal Dialysis

Pros: Similar effectiveness to HD Easy, safe & Cheap

Cons: Higher risk of mechanical obstruction, protein loss in dialysate & ↑BS

ISN 5 R’s Approach to AKI Management

5. Rehabilitation: AKI is associated with late mortality & reduced QoL

F/U 3-6 months post discharge

a) Document recovery or arrange regular F/U if pt has developed CKD

b) Manage complications such as HTN

Conclusions AKI is a common & serious medical emergency world wide AKI has major impact on mortality, GFR recovery & health care cost Apply ISN’s 5 Rs & KDIGO guidelines in prevention & management

1) Risk factors/exposing factors Identified/managed early to avoid AKI

2) Recognition of AKI early is essential to institute therapy early:

Volume resuscitation, Anemia correction, BP/O2 sat optimization

Avoidance of nephrotoxins

3) Response to established AKI: Correct volume status, Control BP/BS, Early nutrition, Sepsis treatment Do not use diuretics to prevent or treat AKI but for volume control Do not use dopamine to prevent or treat AKI

4) RRT: Initiate when indicated & individualize modality (IHD/CRRT/PD) & dose

5) Rehabilitation post discharge with adequate long-term F/U

Limitations of AKI Definitions / Staging: Cannot calculate change in GFR in AKI W/O known baseline Cr Cr is poor indicator of real GFR in unsteady state like AKI Rise in Cr requires time & this delays diagnosis of early injury Cr is affected by:

Muscle mass & muscle dietary supplements Decreased Cr production in CLD Lab techniques / errors Drugs that inhibit tubular secretion (e.g., H2B) Endogenous-Exogenous Chromogens may interfere with assay

Endogenous: Bilirubin, Uric Acid Exogenous: Cephalosporins, Cimetidine, Trimethoprim

Cr might be affected by hemodilution D/T massive blood transfusion or fluid resuscitation & accumulation in acute illness

Estimation of U/O is difficult W/O urinary catheter U/O criterion of 0.5 ml / kg / h for 6h is too sensitive

Rise in Cr is more predictive of mortality than this criterion 0.3 ml/kg/h for 6h correlate better with stage, RRT need & death Morbidly obese pt may fulfill UO criteria W/O GFR change