This document presents a case of acute kidney injury (AKI) in a 74-year-old male farmer who presented with reduced urine output. It provides details on his medical history, examination, initial workup and assessment of AKI likely due to toxic nephropathy, dehydration and possible sepsis. The document then provides an introduction to AKI including definitions, epidemiology, etiology and pathophysiology involving pre-renal, intrinsic and post-renal causes. It also discusses approaches to assessing patients with AKI including history, physical examination and investigations.

1. ACUTE KIDNEY INJURY
Dr. Atere Ahmad Jr

2. OUTLINE
 CASE PRESENTATION
 INTRODUCTION
 EPIDEMIOLOGY
 AETIOLOGY & PATHOPHYSIOLOGY
 ASSESSMENT OF THE PATIENT WITH AKI
 COMPLICATIONS
 PROGNOSIS
 CONCLUSION
 REFERENCE

3. CASE PRESENTATION

4. HISTORY
 Mr. A.F a 74 year old male farmer who presented to the A&E with complaints of
 Reduction in urine output x 7 days
 insidious in onset with no associated hx of frequency, urgency or hesitancy. No
hx of poor stream or terminal dribbling. No dysuria, no hx of vomiting or
diarrhea.
 Patient had a hx of being stung by a swarm of bees 18hrs prior to the onset of
symptoms
 No hx of haematuria, however was noticed to have developed bilateral leg
swelling 3 days prior to presentation as well as hiccups
 There was associated hx of high grade fever that developed a day prior to
presentation

5.  No associated epigastric pain, no hx of irrational talk or excessive somnolence,
no hx of seizures
 No hx of ingestion of herbal medications and no NSAID use
 A known HTN on medication ?drug name
 Not a known diabetic

6. EXAMINATON
 An elderly man, not in any obvious distress, multiple maculopapular, dark
coloured skin lesions on head, face, trunk, upper and lower limbs, afebrile, pale,
anicteric, acyanosed, not dehydrated, with bilateral pitting pedal oedema up to
the knee.
 Cardiovascular
 PR- 68bpm, regularly irregular
 BP- 133/72mmHg
 HS- S1 & S2 only
 Chest
 RR- 20cpm; VBS
 SpO2- 98%, room air

7.  ABDOMEN
 Full, MWR, mild epigastric tenderness
 No palpable organomegally
 CNS
 Conscious and alert; oriented in TPP
 No asterixis; no focal neurologic deficit

8.  ASSESSMENT
 AKI 20 toxic nephropathy/dehydration/sepsis
 BG hypertension
 PLAN
 Urinalysis, FBC, EUCr, RBS, LFT, LDH, serology
 Abdominopelvic USS, ECG
 IVF N/saline 500mls 8-hrly
 IV ceftriaxone 1g 12-hrly
 Tabs NaHCO3 500mg b.d
 IV omeprazole 40mg b.d
 Strict I/O monitoring
 Avoid nephrotoxic drugs

9.  Urinalysis
 Protein 2+
 Blood 3+
 Leucocyte 2+
 Glucose/ketones/nitrite; negative
 pH 8
 E/U/Cr
 Na- 122
 K- 4.4
 Cl- 85
 Ur- 30
 Cr- 1454
 FBC
 WBC 7.2
 Hb 8.6
 PCV 28%
 PLT 303

10.  Reviewed the following day with result of EUCr. Noted to be anuric
 Facial puffiness
 Assessment of AKI 20 to AIN
 Subsequently scheduled for HD
 Amlodopine 5mg dly
 Admitted to the ward
 NaHCO3 increased to 1g b.d

11.  3 episodes of vomiting and 2
episodes of passage of loose stool
 Placed on ORS, Zinc 50mg dly, IV
ondansetron 8mg stat, 4mg b.d
 Developed scrotal oedema
 Torsemide 100mg dly
 Session of HD
 Repeat EUCr
 K- 4.6
 Urea- 16
 Creatinine- 866

12.  Had a total of 3 sessions of HD, and was discharged home.
 To be seen in clinic in one week with results of repeat EUCr, AP-USS,
urinalysis

13. INTRODUCTION

14. INTRODUCTION
 Acute kidney injury (AKI), formerly called acute renal failure, is
commonly considered as an abrupt decline in renal function,
clinically manifesting as a reversible acute increase in nitrogen
waste products—measured by BUN and serum creatinine
levels—over the course of hours to days.
 Resultant failure to maintain fluid, electrolyte and acid-base
homeostasis.

15. DEFINING AKI
 Despite a relative insensitivity to acute changes in GFR, most
definitions of acute renal dysfunction have been based on serum
Cr, either as an absolute value or as a change from baseline.
Other definitions have incorporated urine output (UO) or the
need for dialysis support.

16.  In 2002, the Acute Dialysis Quality Initiative (ADQI) was created to
develop evidence-based guidelines for the treatment and prevention of
AKI, hence the RIFLE criteria was born.
 AKI is stratified into 5 stages, based on severity and duration of
renal injury: Risk, Injury, Failure, Loss, and End-stage disease

18.  In 2004, the Acute Kidney Injury Network (AKIN) was formed and
modified RIFLE to incorporate small changes in sCRr occurring
within a 48h period and to remove changes in GFR as diagnostic
criteria
 Abrupt (within 48hrs) reduction in kidney function currently defined as
an absolute increase in sCr of ≥0.3 mg/dL (≥26.4 μmol/L) or
 A percentage increase in sCr of 50% or more (1.5-fold from
baseline) or
 A reduction in urine output (oliguria of < 0.5 mL/kg/h for >6 h)

20.  The Kidney Disease Improving Global Outcome (KDIGO) defines
AKI as any of the following:
 Increase in sCr by 0.3mg/dL or more within 48 hours or
 Increase in sCr to 1.5 times baseline or more within the last 7 days or
 Urine output less than 0.5 mL/kg/h for 6 hours

23.  There are several biomarkers that are being studied and have
shown to exhibit a great sensitivity and specificity in AKI
diagnosis, a good correlation with RRT requirement, as well as
with mortality
 Neutrophil gelactinase associated lipocalin (NGAL)
 Kidney injury molecule (KIM-1)
 Interleukin-6, -8, and -10
 Cystatin-C
 N-acetyl-β-glucosaminidase (NAG)
 Liver fatty acid binding protein
 Retinol binding protein
 Matrix
metalloproteinase-9
 Proatrial natriuretic
peptide
 Neutrophil CDIIb
 α-Glutathione -S-
transferase (GST)

24. EPIDEMIOLOGY

25. EPIDEMIOLOGY
 AKI is common, occurring in up to 18% of hospitalized patients
 An independent risk factor for mortality
 In a study in Lagos, sepsis was by far the most common cause of AKI
accounting for 50% of all cases followed by obstructive nephropathy and
gastroenteritis.

27. AETIOLOGY & PATHOPHYSIOLOGY

28. The hydrostatic pressure gradient across the glomerular
capillary wall is the primary driving force for glomerular
filtration
Autoregulation helps protect the glomerular capillary from
sudden changes in systolic pressure
Autoregulation of glomerular filtration is the result of
three major factors that modulate either afferent or
efferent arteriolar tone: these include
myogenic reflex in the afferent arteriole,
tubuloglomerular feedback, and
angiotensin II-mediated vasoconstriction

29. AETIOPATHOGENESIS
 The causes of AKI have traditionally been divided into three broad
categories
 Pre-renal AKI
 Intrinsic renal AKI
 Post-renal AKI

30. RISK FACTORS
 Elderly
 Male sex
 CKD
 Cardiac failure
 Peripheral vascular disease
 CLD
 DM
 Drugs (NSAIDs ACEI)
 Sepsis
 Poor fluid intake/increased losses

31. PRE-RENAL AKI
 Pre-renal AKI is the most common form of AKI. It is the designation for a rise
in sCr or BUN concentration due to inadequate renal plasma flow and
intraglomerular hydrostatic pressure to support normal glomerular filtration.
 Accounts for about 40 to 70% of AKI

32.  By definition, prerenal AKI involves no parenchymal damage to the kidney and
is rapidly reversible once intraglomerular hemodynamics are restored.
 It may coexist with other forms of intrinsic AKI associated with processes
acting directly on the renal parenchyma.
 Prolonged periods of prerenal azotemia may lead to ischemic injury, often
termed acute tubular necrosis (ATN)

33.  Volume depletion
 Haemorrhage
 Burns
 Renal losses (polyuria, diuresis)
 Dehydration
 GI fluid losses (vomiting, diarrhea)
 Decreased effective circulatory blood
volume
 Cardiac output (CCF, hypotension,
arrhythmia, MI)
 Liver failure
 Sepsis (vasodilation)
 Impaired renal autoregulation
 NSAIDs
 ACEIs
Causes of prerenal AKI include:

34. INTRINSIC RENAL AKI
 10-50% of AKI cases
 Structural damage to renal parenchyma
 Tubular
 Glomerular
 Interstitial
 Vascular

35.  Tubular damage
 Acute tubular necrosis (commonest renal cause of AKI)
 Ischemia; hypotension, sepsis
 Endogenous nephrotoxins; haemoglobin, uric acid, rhabdomyolysis, myeloma
 Exogenous toxins; aminoglycosides, radiological contrast, amphotericin B,
cisplatin
 Glomerular damage
 Nephrotic/Nephritic glomerulonephritis
 Autoimmune; SLE, HSP
,
 Drugs, Infections

36.  Interstitial damage
 Allergic (rifampin, etc.)
 Infection (severe pyelonephritis, Legionella, sepsis)
 Infiltration (lymphoma. leukemia)
 Inflammatory (Sjogren’s, tubulointerstitial nephritis uveitis), sepsis
 Vascular damage
 Small vessels
 Glomerulonephritis, vasculitis, TTP/HUS, DIC, atheroemboli, malignant HTN,
calcineurin inhibitors, sepsis
 Large Vessels
 Renal artery embolus, dissection, vasculitis
 Renal vein thrombosis, Abdominal compartment syndrome

37. POST-RENAL AKI
 Results from obstruction of urinary outflow
 Accounts for 10-25% of AKI
 Luminal: stones, clots, sloughed papillae
 Mural: neoplasm (e.g ureteric, bladder, prostrate), BPH, strictures
 Extrinsic: pelvic malignancy, retroperitoneal fibrosis
 Rapid resolution of post-renal AKI without structural damage restores kidney
function.

39. ASSESSMENT OF THE PATIENT WITH AKI

40. HISTORY
 AKI has a long differential diagnosis. Adequate hx can help classify the
pathophysiology of AKI as pre-renal, intrinsic, or post-renal failure, and may
suggest some specific aetiologies
 Pre-renal AKI
 Commonly present with symptoms of hypovolemia; decreased urine output,
thirst, dizziness, orthostatic hypotension
 Elicit hx of volume loss from vomiting, diarrhea, polyuria, haemorrhage.
 Hx of orthopnoea, PND in advanced cardiac failure

41.  Intrinsic renal AKI
 Patients can be divided into those with glomerular etiologies and those with
tubular etiologies of AKI
 Nephritic syndrome of hematuria, edema, and hypertension indicates a
etiology for AKI (hx of previous sore throat or skin infections)
 Acute tubular necrosis (ATN) should be suspected in any patient presenting after
period of hypotension secondary to cardiac arrest, hemorrhage, sepsis, drug
overdose, or surgery.
 Elicit hx of exposure to nephrotoxins; current medications and any recent
radiologic examinations
 Pigment-induced AKI should be suspected in patients with possible
rhabdomyolysis (muscular pain, seizure, excessive exercise)
 Allergic interstitial nephritis should be suspected with fevers, rash, arthralgias,
exposure to certain medications, including NSAIDs and antibiotics.

42.  Post-renal AKI
 Suspected in older men with symptoms of urgency, frequency, and
hesitancy (prostatic obstruction)
 A history of prior gynecologic surgery or abdominopelvic malignancy
 Flank pain and hematuria should raise a concern about renal calculi or
papillary necrosis as the source of urinary obstruction.
 Certain medications could be pointers of crystal nephropathy causing
tubular obstruction. The use of acyclovir, methotrexate, triamterene,
indinavir, or sulfonamides implies the possibility that crystals of these
medications have caused tubular obstruction.

43. EXAMINATION
 Physical examination can give rise to important clues in diagnosing the
aetiology
 Skin
 Eyes
 Cardiovascular system
 Abdomen
 Pulmonary system

44.  Skin
 Skin tugor (hypovolemia)
 Livido reticularis, digital ischemia,
butterfly rash, palpable purpura -
Systemic vasculitis
 Maculopapular rash - Allergic
interstitial nephritis
 Eyes
 Jaundice - Liver diseases
 Band keratopathy (i.e.,
hypercalcemia) - Multiple
myeloma
Purpura
Band
keratopathy

45.  Cardiovascular system
 Tachycardia, reduced jugular venous pressure in pre-renal AKI
 Irregular rhythms (ie, atrial fibrillation) - Thromboemboli
 Pericardial friction rub - Uremic pericarditis
 Increased jugulovenous distention, rales, S 3 - Heart failure
 Severe hypertension with renal failure may suggest renovascular disease,
glomerulonephritis

46.  Abdomen
 Pulsatile mass or bruit - Atheroemboli
 Abdominal or costovertebral angle tenderness - Nephrolithiasis, papillary
necrosis, renal artery thrombosis, renal vein thrombosis
 Pelvic, rectal masses
 Palpable kidneys
 Distended bladder – Urinary obstruction
 Tense ascites; compartment syndrome

47. INVESTIGATIONS
 Urine tests
 Urinalysis!! Dipstick can suggest infection (leucocytes + nitrites);
glomerular disease (blood + protein)
 Urine microscopy for casts, crystals and cells. Culture for infection
 Blood tests
 E&U, FBC, LFT, clotting, ESR
 Culture blood if signs of infection

48.  Imaging
 Renal USS; obstruction, hydronephrosis, cysts, small kidneys, masses
 Assess corticomedullary differentiation
 CXR if signs of fluid overload
 Kidney biopsy
 If cause of AKI not apparent based on clinical context, physical
examination, lab & radiologic studies and pre-renal, post-renal and
ischemic or nephrotoxic AKI has been deemed unlikely, and other
possibilities are being considered (glomerulonephritis, vasculitis etc.)

49. PRINCIPLES OF MANAGEMENT OF AKI
 General measures (fluid & electrolyte balance)
 Treat underlying cause
 Manage complications
 Renal replacement therapy

50. GENERAL MEASURES
 Maintain fluid homeostasis and electrolyte balance
 Limit fluid intake to insensible loss and ongoing loss if euvolaemic
 Avoid K+-containing fluids unless hypokalemic ; supplements and K+
sparing diuretics
 Stop nephrotoxic drugs
 NSAIDs, gentamicin, nitrofurantoin
 Adjust doses of renally excreted drugs
 Contrasts; ensure adequate hydration pre and post procedure

51. TREAT UNDERLYING CAUSE
 Pre-renal
 Correct volume depletion with appropriate fluids
 Treat sepsis with appropriate antibiotics
 Ionotropic support if signs of shock
 Post-renal
 Catheterize and consider CT of renal tract
 Refer to urologist if obstruction likely cause (consider stent/nephrostomy
insertion)
 Intrinsic renal
 Evaluate and manage underlying cause as appropriate

52. MANAGE COMPLICATIONS
 Hyperkalaemia
 Pulmonary oedema
 Uraemia
 Acidaemia
 Cardiac complications; arrhythmia,
pericarditis, pericardial effusion
 Malnutrition
 Hypovolemia

53. RENAL REPLACEMENT THERAPY
 Indications for haemodialysis in AKI
 Clinical
 Biochemical

54.  Uraemic complications
(encephalopathy, pericarditis,
myopathy, neuropathy, gastritis)
 Refractory pulmonary oedema
 Drug overdose (lithium,
barbiturates, ethylene glycol,
salicylates, theophylline)
 Refractory hypertension
 Anuria
Clinical indications

55.  Hyperkalemia >6mmol/L
 BUN >100mg/dl
 Severe metabolic acidosis; pH <7.2
 Hypermagnesaemia >4.0mmol/L
Biochemical indications

56. PROGNOSIS
 The development of AKI is associated with a significantly increased risk of in-
hospital and long-term mortality, longer length of stay, and increased costs.
 Pre-renal AKI, with the exception of the cardiorenal and hepatorenal
syndromes, and post-renal azotemia carry a better prognosis than most
cases of intrinsic AKI
 The kidneys may recover even after severe, dialysis-requiring AKI. Survivors
of an episode of AKI requiring temporary dialysis, however, are at extremely
high risk for progressive CKD, and up to 10% may develop end-stage renal
disease

57. CONCLUSION
 AKI is a syndrome that rarely has a sole and distinct pathophysiology.
 Many patients with AKI have a mixed aetiology where the presence of sepsis,
ischaemia and nephrotoxicity often co-exist and complicate recognition and
treatment.
 Furthermore the syndrome is quite common amongst patients without
critical illness and it is essential that health care professionals, particularly
those without specialization in renal disorders, detect it easily.

58. …...the ghost of deceased patients that haunt us, do not
ask why we did not employ the latest fad of clinical
investigations. But they ask “Why did you not test my
Urine?”
Sir Robert Hutchinson
(1871- 1960)

59. REFERENCE
 Harrison’s principle of Internal Medicine
 Oxford handbook of internal medicine
 Schrier RW, Wang W, Poole B, Mitra A. Acute renal failure: definitions, diagnosis,
pathogenesis, and therapy. J Clin Invest. 2004 Jul. 114(1):5-14. [QxMD MEDLINE
Link]. [Full Text].
 Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney
Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit
Care. 2007. 11(2):R31. [QxMD MEDLINE Link]. [Full Text].
 Ricci Z, Cruz D, Ronco C. The RIFLE criteria and mortality in acute kidney injury: A
systematic review. Kidney Int. 2008 Mar. 73(5):538-46. [QxMD MEDLINE Link].

60. Thank you