1. Acute Kidney Injury (AKI) KDIGO Clinical Practice Guidelines
Ali AlSahow

2. Introduction Common & serious medical emergency characterized by:
Rapid decline in GFR that evolves over hrs-days-wks
Retention of waste products & dysregulation of ECV & electrolyte
Oliguria with U/O 0.5 ml/min/d complicates 50% of cases
High mortality rate with high rate of development or progression of CKD

3. Historical Background of AKI
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

4. Definition & Staging of AKI
Stage
Cr criteria
UO criteria 1
Increase in Cr by ≥26.5 µmol/l within 48hrs OR 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 Cr OR 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

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

6. Pattern of AKI & Country Income
High & Most Middle Income Countries:
Well developed health care systems & optimal renal services
Occurs mainly in ICU
Associated with MOF
D/T sepsis, trauma or surgery
Affects mainly the elderly
Difficult to prevent
Expensive to treat
Low & Some Middle Income Countries:
Poorly developed health care system & poor renal services
Seen in Various hospitals (1o, 2o, 3o) & various hospital units
MOF less common
D/T infections or diarrhea
Affects Mainly young otherwise healthier subjects
Preventable
Inexpensive to treat if detected early but too costly for pt if detected late

7. Outcome of AKI
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

9. Etiology 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

10. Complications of AKI Hyperkalemia with risk of malignant arrhythmias
Metabolic Acidosis decreasing CO & gut barrier function
Hyperphosphatemia & Hypocalcemia
Volume overload causing Pulmonary edema & Hypertension
Delayed wound healing
Anemia
Bleeding tendency D/T plt dysfunction
Increased risk of infections D/T WBC dysfunction
Encephalopathy / Pericarditis / Tamponade
Stress GI ulcers
Compromised investigations by contraindicated contrast
Compromised management by contraindicated drugs

11. ISN 5 R’s Approach to AKI Management
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

12. Risk Factors for AKI Non-modifiable: Potentially modifiable:
Old age
Male sex
Black race
Comorbidities:
Pre-Existing CKD DM
HTN
CLD / IBD
CHF / CAD / Recent MI
PAD
COPD
Malignancy
Potentially modifiable:
Anemia / Hypoxemia
Sepsis
Trauma
Contrast / Nephrotoxic drugs
Volume status
Volume Depletion
Volume Overload
Using colloids / Cl rich fluids
Surgery:
Cardiac surgery
Major non-cardiac surgery
Emergency procedures
Environmental Factors:
Poor Sanitation & No clean water
Poor control of parasites & vectors
Infrastructural Factors:
Poor HC budget & Services
Poor Transportation

13. Exposure to be avoided in high risk pts
High & Most Middle Income Countries:
Sepsis
Circulatory shock
Trauma & Burns
Cardiac Surgery & Major non – cardiac Surgeries
Nephrotoxic Drugs & Agents
Low & Some Midle Income Countries:
Diarrhea
Obstetric Complications Including septic abortion
Infections: Malaria, Leptospirosis, Dengue Fever, Cholera
Animal Venoms: Snakes, Wasps, Spiders
Natural medicines & Natural dyes
Prolonged Heavy Physical Work in Unhealthy Environment

14. ISN 5 R’s Approach to AKI Management
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

15. ISN 5 R’s Approach to AKI Management
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

16. Identify the cause of AKI & start specific therapy
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
Correction of K / HCO3 / Ca / PO4 / Uric acid disorders
Use NaHCO3 cautiously to avoid volume overload & hypernatremia
Adequate BS control to keep BS lowers mortality
Search for & aggressively treat infections with antibiotics
ESA for anemia
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 Kca/kg/d is advised for any stage of AKI
Adjust doses of drugs that are renally excreted or protein-bound
Avoid nephrotoxins: Dye, aminoglycosides, ampho B, NSAIDs
Assess the need for urgent RRT

17. 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 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

18. 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

19. 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:
Return of MAP to ≥ 65 mmHg
CVP between 8-12 mmHg
Improvement in blood lactate level
Central Vein Oxygenation Saturation > 70%
UO ≥ 0.5 ml/kg/hr
EGD septic shock resuscitation had no impact on outcome - NEJM

20. 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:
Reduced ATPase activity & renal tubular O2 consumption may decrease ischemic damage of vulnerable outer medullary tubules
Increased UO may wash out necrotic debris blocking tubules
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

21. Dopamine – Receptor Agonists
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
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

22. Referral to Nephrologist
AKI in renal transplant pt
AKI complications
AKI stage 3
AKI on CKD stages 3/4
Resolved AKI with residual impaired GFR, HTN or Proteinuria
AKI of unknown etiology
AKI not responding to therapy
Remember:
Density of physicians in many African countries is /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

23. ISN 5 R’s Approach to AKI Management
Renal Replacement Therapy in AKI:
Timing of Initiation, Modality, Dose & Duration of RRT

24. Timing of RRT in AKI Urgent Indications
Severe K not responding to therapy
Severe acidosis (pH <7.1) not fixed by NaHCO3 used for volume restoration
Uremic Encephalopathy
Uremic Pericarditis
Severe pulmonary edema not responding to diuresis
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?

25. Timing of RRT in AKI Non – Urgent Indications
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)

26. 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

27. Conventional Intermittent HD Advantages
Cheap & low work load
Small amount of anticoagulation required
Intermittent nature allows diagnostic & therapeutic procedures
3-4 sessions per wk & 3-4 hrs per session
Adequate removal of excess fluid by UF
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 ml/min) & Qd (above ml/min)
Using large (high efficiency) & porous (high flux) membrane

28. Conventional Intermittent HD Disadvantages
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

29. CRRT Advantages 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

30. CRRT Disadvantages
Expensive with use large amounts of substitution fluids
High work load with 24h operation
Requires heavy anticoagulation
Pt immobilization
Downtime may cause loss of expensive disposables
Loss of nutrients, vitamins & trace elements
Different drug clearance & dosing & affected by downtime
Hypothermia?
? Removal of useful anti-inflammatory molecules

31. Alternative Modalities
Extended Daily Dialysis (EDD):
Good IHD clearance plus gentle CRRT fluid & solute removal
Conventional dialysis machine with Qb 200ml/min & Qd 300ml/min
Runs for long periods (6-12hr/d) allowing investigations / procedures
Less anticoagulation & faster correction of acidosis than CRRT
Pulse high volume (HV) CVVHF:
CRRT for AKI in septic pts with MODS
Removes middle & large MW inflammatory mediators
UF rate of 85ml/kg/hr for 6-8hrs
Followed or preceded by UF rate of 35ml/kg/hr
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

32. 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 ml/kg/h for CRRT – 42L/d

33. Peritoneal Dialysis Pros: Cons: Similar effectiveness to HD
Easy, safe & Cheap
Cons:
Higher risk of mechanical obstruction, protein loss in dialysate & ↑BS

34. ISN 5 R’s Approach to AKI Management
Rehabilitation:
AKI is associated with late mortality & reduced QoL
F/U 3-6 months post discharge
Document recovery or arrange regular F/U if pt has developed CKD
Manage complications such as HTN

35. 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
Risk factors/exposing factors Identified/managed early to avoid AKI
Recognition of AKI early is essential to institute therapy early:
Volume resuscitation, Anemia correction, BP/O2 sat optimization
Avoidance of nephrotoxins
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
RRT:
Initiate when indicated & individualize modality (IHD/CRRT/PD) & dose
Rehabilitation post discharge with adequate long-term F/U

38. 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