Acute Kidney Injury epidemiology, pathophysiology and management based on current evidence. The presentation is suitable for internal medicine trainees and nephrology fellows.

1. Core Series: Acute Kidney Injury
Part 1
Adeel Rafi Ahmed
MB BCh BAO MRCPI MRCP(UK) PGDip (ClinEd)
Holder of European Certificate in Nephrology and European Speciality Exam in Nephrology
Renal Registrar
Adjunct Clinical Lecturer UCC
University Hospital Waterford, Ireland

2. By the end of the tutorial you will be able to :
• Recall the basic definition, classification, and epidemiology of acute kidney
injury ( AKI)
• Generate a differential diagnosis when approaching a patient with AKI
• Identify risk factors for AKI
• Initiate basic workup for AKI
• construct basic management of AKI
• Identify when to escalate to Nephrology department
• Identify indications for renal replacement therapy ( RRT)
• Manage complications of severe AKI
• Prognosis of AKI

3. What is the definition of AKI?
•A broad clinical syndrome defined by an
abrupt decrease in kidney function over
a period of hours to days characterised
by rise in serum creatinine or a
decrease in urine output.
Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet 2012;380:756-66.

4. How do we classify and stage AKI?
Khwaja A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron
Clinical Practice 2012;120:c179-c84.

5. What is the epidemiology of AKI?
• Incidence
• up to 20% of hospitalised adult patients
• Up to 50% of ICU admissions
• Mortality
• Upto 15% in non ICU patients
• Up to 50% in ICU patients.
• Prognosis
• Increased incident of CKD and ESRD
• Other organ dysfunctions ( increased incidence of cardiovascular disease )
• Should patient be re evaluated post DC after AKI? Yes within 3months.
Hoste EAJ, Kellum JA, Selby NM, et al. Global epidemiology and outcomes of acute kidney
injury. Nature reviews Nephrology 2018;14:607-25.

6. What are risk factors for AKI?
• Age > 65
• Diabetes
• CKD
• Heart failure/ chronic liver disease
• Sepsis
• Preoperatively particularly cardiovascular surgery
• Medication that influence renal blood flow or volume status such as ACE-I
or ARBS or Diuretics or NSAIDS
• On medications that can be toxic to renal tubules ( Aminoglycosides)
• Getting Contrast particularly if dehydrated, hypovolemic or hypervolemic
Lewington A, Kanagasundaram S. Renal Association Clinical Practice Guidelines on acute kidney injury.
Nephron Clinical practice 2011;118 Suppl 1:c349-c90.

7. Prevention of AKI
• Key: optimise volume status. Don’t overfill or underfill.
• Identify any potential nephrotoxic drugs that can be avoided
• Stop any drug that will affect renal autoregulation of perfusion prior to
kidney stressing procedure ( preoperative) eg NSAIDS, ACE-I/ARB.
Metformin can be continued if egfr> 30 prior to contrast. Some protocols
suggest stopping it for 48hrs post contrast administration in high risk
patients.
• No proven benefit of giving 0.9% saline or isotonic bicarbonate to everyone
with CKD prior to Contrast administration. Important is patient is
euvolaemic. No role for N-acetylecysteine.
• Use local hospital protocol.
Weisbord SD, Gallagher M, Jneid H, et al. Outcomes after Angiography with Sodium Bicarbonate and
Acetylcysteine. N Engl J Med 2018;378:603-14.

8. How will you generate a differential diagnosis
when approaching a patient with AKI?
AKI
PreRenal
1-Intravascular
volume depletion
2-Decreased
effective arterial
circulation
3-systemic or
renal
vasodilaton
4-Impaired
renal
autoregulation
Intrinsic Renal
Vascular glomerulus Interstitial
Tubular
Ischaemic vs
toxin
Post Renal
ATN
Toxin
-Contrast
-
rhabdomyolysi
s
Myeloma
Tumour lysis
syndrome
Acute GN
IgA
SLE
MPGN
Post
infectious
AIN
-Drugs
-infections
Autoimmune(
sarcoid/sjogre
ns)
malignancy
-Thrombotic
microangiopat
hy (TTP/HUS)
-Vasculitis
-Hypertenive
emergency
- Renal artery
stenosis/
thrombosus/
artheroemobli

9. How frequently does pre-intrinsic-post renal AKI occur in hospital setting?
‘Pre-renal AKI
and ischaemic
acute tubular
necrosis are
continuum of
same
pathophysiologic
al process. These
two account for
75% of AKI’
Singri N, Ahya SN, Levin
ML. Acute renal failure.
Jama 2003;289:747-51.

10. How frequently does pre-intrinsic-post renal AKI occur in hospital setting?
• “The most frequent causes of ARF were ATN (45%), prerenal (21%),
acute-onset chronic renal failure (12.7%) and obstructive ARF (10%)”
• “16% were attributed to medications that were either nephrotoxic,
causes of interstitial nephritis, or causes of hemodynamic changes
resulting in an increased serum creatinine level.”
Liaño F, Pascual J. Epidemiology of acute renal failure: a prospective, multicenter, community-based study.
Madrid Acute Renal Failure Study Group. Kidney Int 1996;50:811-8.
Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis
2002;39:930-6.

11. What is the pathophysiology of pre renal AKI
and AKI secondary to ATN?
• Ischaemia due to prolonged renal hypoperfusion ( pre-renal ) causes
acute tubular cell damage.
• Kidneys can maintain glomerular filtration with a low MAP range of
65-85mmHg through autoregulatory mechanisms.
• Patients with prior vascular disease/chronic htn usually require higher
end of the MAP range to maintain renal perfusion.
Kato R, Pinsky MR. Personalizing blood pressure management in septic shock. Annals of Intensive Care
2015;5:41.

12. What is the pathophysiology of pre renal AKI
and AKI secondary to ATN?
1- As renal arterial pressure decreases ( within
autoregulatory range 65-85mmHg)
i- afferent arteriole vasodilates via renal
prostaglandins
Ii- efferent arterioles vasconstrict via low dose
endogenous angiotensin II
Iii- this maintains GFR and glomerular capillary
pressure
2-Once renal arterial pressure below autoregulatory
range
i- endogenous vasoconstrictors ( noradrenaline,
sympathetic system, angiotensin II high dose)
released which causes increased afferent
arteriole resistance and decrease glomerular
capillary pressure)
Ii- If above state is prolonged ischaemic ATN
develops.

13. How to assess a patient with AKI?
• HISTORY: Majority of Cases in hospital PRE RENAL/ATN or Drug
Related
• Categorise as per KDIGO. Good to establish oligouric vs non oligouric
• Past medical History/ Risk Factors for AKI : >65 age / CKD / CCF/ Liver
disease/ DM/ Vascular Disease/ Multiple Myeloma/ Others (please
specify
•
Volume
Status
BP
Dry Euvolemic Hypervolaemic Not assessed
Fluid Input and
output chart
Available/
Maintained
Requested N/A N/A
Daily weights Available/maint Requested N/A N/A

14. What non imaging investigations you can
request?
1- VBG : K+ / HCO3 / pH / Lactate / Anion gap
2- Urine Dipstick: Blood ( bleeding glomeruli) and protein indicative of
intrinsic Renal pathology. Leukocyte nitrite urosepsis?
3- MSU for Casts: -
-RBC Casts/ Dysmorphic RCC bleeding inflamed Glomeruli GN
- White Cell Cast: Pyelonephritis/ AIN
- Eosinophillic casts: AIN/ Cholestrol thrombi
- Hyaline casts: dehydration
- Fatty Casts: nephrotic syndrome/ maltese cross sign under polarised light
- Granular muddy brown cast: ATN
- Bland: ATN/AIN/ anything.

15. Investigations continued
• 4- Urine Biochemistry:
• Urinary Sodium < 20 prerenal
• Fractional excretion of Na <1% prerenal
• Fractional of excretion of Urea < 35% use when on diuretics pre renal
• Urine specific Gravity > 1.020 prerenal.
• 5- Urine Protein: Cr ratio /Alb:Cr
• 6- Spep/Upep
• 7- Vasculitic Screen ( ANA/ANCA/RF/ C3,C4) if history and biochemistry
(KDIGO-3) indicative
• HIV/HEP B/HEP C
• Blood Film/CK/ CRP/ Plasma Viscosity/ ESR

16. Review MED
• Nephrotoxic Medications
• Eg: (ACE-I/ARB/ Diuretics/ NSAIDS/ New antimicrobials including
antivirals or medication ( penicillin, aminoglycosides, vancomycin)/
Allopurinol/ PPI/ Metformin ( not renal toxic however contraindicated
below eGFR of 30 due to increase risk of lactic acidosis) , LMWH,
opioids
• Dose Adjust as appropriate and stop toxic agents
• IV contrast in the last 24-72hrs
• (Avoid if eGFR< 30 or rapidly declining unless lifesaving/ essential for
further management)

17. What imaging studies should be used?
•Renal US:
• Relative indications: decrease Urine Output/ urological
patient/malignancy/ AKI not recovering/ No cause obvious from initial
assessment) and perform within 24hrs or within 6hrs if obstruction with
infection suspected
• How to distinguish AKI from CKD?
• Most accurate way is to see previous Cr over last 3months and compare ( but not
always available)
• Radiological: In CKD kidneys are usually small on ultrasound with poor/decreased
corticomedullary differentiation
• Biochemical: In progressive CKD generally anaemia will be more pronounced, low
calcium, elevated phosphate, elevated PTH. However all can exist in severe AKI.
• CTKUB

18. How to relatively Confirm Diagnosis when Renal
function deteriorating despite optimum
treatment?
•RENAL Biopsy
• Unexplained AKI
• Suspected glomerular disease( hematuria/ significant
proteinuria)
• Suspected systemic Disease ( ANCA/Lupus etc)
• Likely to influence Treatment/ prognosis/ identify
disease activity.

19. Current Creatinine + establish baseline Cr
VBG for urgent K+HC03+pH
Urine dipstick +document
results+MSU+uPCR+ uNA/uCR/uUREA
Stop Nephrotoxins
Establish Urine output if available
Monitor fluid input and output
Assess and optimize volume
Consider a renal ultrasound
Treat underlying aetiology (CCF/sepsis
hypoperfusion/Toxins/obstruction/primary
renal disease)
K 6 : treat as per hyperkalemia protocol
If dipstick +ve for protein, blood or both ->
send renal immunological screen -> ANA,
ANCA, C3C4, SPEP , SFLC, RF, ANTI
GBM , Hep b/C/HIV/CK/blood film
Hydronephrosis  consult urology

20. Ostermann M, Joannidis M. Acute kidney injury 2016: diagnosis and diagnostic
workup. Critical Care 2016;20:299.

21. What questions to ask Every time?
• What is the creatinine?
• What is the baseline creatinine?
• What is the Pottassium?
• What is the pH and HCO3?
• What is the UO?
• What is the Urine dipstick?
• What is the volume status? Pulmonary edema?
• What is the Blood Pressure?

22. What are the indications of renal replacement
therapy?
• Conventional indications for renal replacement therapy ( dialysis )
• 1.1. Fluid overload resistant to diuretic therapy
• 1.2. Metabolic acidosis (pH < 7.15) refractory to medical management
• 1.3. Hyperkalaemia (K > 6.5 mEq/L) refractory to medical management
• 1.4. Uraemic symptoms or signs (encephalopathy, pericarditis, and bleeding diathesis)
• Other important indications for RRT
• 1.5. Poisoning with a dialyzable drug or toxin (Barbiturates, lithium, Alcohol,
salicylates, theophylline- BLAST )
• 1.6. Hyperthermia refractory to regular cooling techniques
• 1.7. Life-threatening electrolyte derangements in the setting of acute kidney injury
• 1.8. Progressive azotaemia or oliguria unresponsive to medical management
Ahmed AR, Obilana A, Lappin D. Renal Replacement Therapy in the Critical Care Setting. Crit Care Res Pract
2019;2019:6948710-.

23. What type of Renal replacement therapies
are available acutely?
• Intermittent haemodialysis (IHD)
• Blood pressure needs to be stable generally
• Can be done at ward level
• Continuous Renal Replacement Therapy ( CRRT)
• Done in ICU
• For haemodynamically unstable patient
• Slower removal of fluid and toxin
• Acute peritoneal dialysis
• Rarely done in UK and Ireland
• Was considered in COVID 19 pandemic due CRRT replacement fluid being out
of stock, specialist nurses off sick, lack of enough machines.
Ahmed AR, Obilana A, Lappin D. Renal Replacement Therapy in the Critical Care Setting. Crit Care Res Pract
2019;2019:6948710-.

24. When to definitely involve nephrology?
• Active urinary sediments ( protein + blood on urine dipstick ) + AKI
• AKI KDIGO stage 3 or meeting criteria to initiate renal replacement
therapy (dialysis )
• Non resolving AKI after 24 hr to 48hrs after achieving euvolemic state

25. Common Complications associated with AKI
• Hyperkalaemia and other electrolyte abnormalities ( increased
phosphate)
• Pulmonary oedema in oliguric AKI / or and Heart failure ( cardiorenal
syndrome)
• Metabolic Acidaemia (pH<7.35, HCO3< 22mmol/L )
• Encephalopathy/pericarditis/serositis

26. Hyperkalaemia: Principles of management
• Serum K+> 6mmol/L
• Stop any drug that can worsen hyperkalaemia. ( ACE-I/ ARB, K+ sparing diuretics)
• Stabilise cell membrane
• Particularly cardiac cell membrane objectively seen with ECG changes such prolonged PR, tall tented T waves,
widening QRS complex, heart block
• TX: Calcium Gluconate 10% 10ml over 2-10mins. Onset 2-3mins, Duration of action 45mins. Can be repeated
again.
• Shift potassium from extracellular to intracellular space
• 5-10units insulin ( actrarapid ) with 50%dextrose in 50ml over 30mins.
• Check glucose every 30mins for 4-6hrs.
• Lasts 4-6hrs.
• High dose salbutamol nebuliser have similar function (10mg qds)
• Removing Potassium from extracellular space
• If hypovolaemic : volume resuscitate with isotonic (0.9%) saline or isotonic (1.26% sodium bicarbonate ( if pH
<7.30 and no contraindication, done under senior supervision)
• Volume resuscitation will increase glomerular capillary pressure and also Na+ is exchanged for K+ in distal
tubule I.e sodium absorbed potassium excreted
• If Hypervolemic and blood pressure stable: Furosemide high dose (2X baseline dose or 1mg/kg in diuretic naïve)
• Can consider calcium resonium ( note works in 24 to 48 hrs and contraindicated in bowel obstruction)
• Renal replacement therapy ( IHD/CRRT) if medical treatment fails.
Coutrot M, Dépret F, Legrand M. Tailoring treatment of hyperkalemia. Nephrol Dial Transplant 2019;34:iii62-
iii8.

27. Pulmonary Oedema and AKI
• Mortality > 50%
• Not only due to fluid retention but also due to inflammation
• Principle of management
• LMNOP
• Loop diuretics ( furosemide ) : high dose as low albumin and low GFR decreases its
efficacy and potency. 2-2.5X baseline dose or 1-1.5mg/kg or infusion (eg 240mg/24hrs).
Only used to treat hypervolaemia, no direct role in prevention of AKI or renal function
recovery.
• +- morphine for vaso and venodilation
• Oxygen
• Nitrates
• Position upright.
• Respiratory compromise/hypoxic and oliguric despite diuretics? Renal
replacement therapy ( IHD/ CRRT)
1-Patschan D, Patschan S, Buschmann I, Ritter O. Loop Diuretics in Acute Kidney Injury Prevention, Therapy, and
Risk Stratification. Kidney and Blood Pressure Research 2019;44:457-64.
2-Felker GM, Lee KL, Bull DA, et al. Diuretic Strategies in Patients with Acute Decompensated Heart Failure. New
England Journal of Medicine 2011;364:797-805.

28. What fluid would you use in AKI?
• Crystalloid (0.9% saline/hartmanns/1.26% bicarb/plasmalyte) vs
Colloid ( 5% albumin/ gelofusion/FFP ) ?
• Use crystalloids. Gelofusion ( starch based ) associated with worse outcomes
particularly AKI and need for RRT.
• 5% albumin in hepatorenal syndrome 1g/kg/24hrs.
• OK, So which crystalloid?
• Use Balanced crystalloid comparatively to 0.9% saline
• Limited evidence suggest lower incidence of AKI
• 0.9% saline is chloride rich  worsens acidosis due to hyperchloraemia which can also
worsen renal cortical tissue perfusion
• However main aim is to attain euvolaemia and haemodynamic stability thus initial
resuscitation should not be delayed due to decision on hartmann vs normal saline!
Lewis SR, Pritchard MW, Evans DJ, et al. Colloids versus crystalloids for fluid resuscitation in critically ill
people. The Cochrane database of systematic reviews 2018;8:Cd000567.
Ding X, Cheng Z, Qian Q. Intravenous Fluids and Acute Kidney Injury. Blood Purification 2017;43:163-72.

30. When can I use isotonic sodium bicarbonate
in AKI?
• 1.26% sodium bicarbonate= 5% Dextrose 850ml + 8.4% Sodium
bicarbonate 150ml= 1L isotonic sodium bicarbonate= 150mmol/L of
sodium + 150mmol/L bicarbonate
• Can be considered in severe AKI + acidaemia ( ph<7.3)+ HCO3<22mmol/L
+- hyperkalaemia
• Don’t use for initial resuscitation and always try to correct the underlying
pathology
• Relative contraindications: as for any IV fluid i.e volume overloaded,
hypocalcaemic ( bicarbonate decrease ionised calcium), respiratory
acidosis, not used in Ketoacidosis unless pH< 7.0
• Potentially reduce the need for RRT.
• Use under supervision of a senior clinician or Renal team
Jaber S, Paugam C, Futier E, et al. Sodium bicarbonate therapy for patients with severe metabolic acidaemia
in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet
2018;392:31-40.

31. The Big Picture
• AKI : 1.5X Cr rise acutely/ UO <0.5ml/kg/hr for 6 or more hours
• Conventional classification : Pre renal/intrinsic renal/post renal
• Pre renal and prolonged pre renal injury leading to ATN accounts for majority of in
patient AKI
• Urine dipstick and volume assessment crucial in management of AKI
• AKI + +urine dipstick for blood and protein consider intrinsic renal screen and Renal
consult
• Consider Renal US to out rule obstruction ( post renal )
• Urgent management of hyperkalaemia and pulmonary oedema is required and
where medical treatment fails dialysis or other forms of renal replacement therapy
will be required.
• High dose diuretics are usually required in treating pulmonary oedema with AKI
• Isotonic crystalloids ( 0.9% saline/ balanced crystalloid ( hartmanns) } are fluid of
choice for volume resuscitation. Some literature supports use of balanced crystalloid
over isotonic saline.