Slide showing the pathology of acute kidney injury, its diagnosis, investigations and its management.

1. ACUTE KIDNEY INJURY
BY:
DANIEL DENNIS YISHENG M.D
BARAU DIKKO TEACHING HOSPITAL
KADUNA STATE UNIVERSITY
NIGERIA.

2.  Introduction
 Epidemiology
 Classification
 Clinical features
 Signs & Symptoms
 Diagnosis
 Differential Diagnosis
 Investigations
 Complications
 Treatment
 Clinical course & prognosis
 Prevention
 Summary
OUTLINE

3.  Acute renal failure (or Acute kidney injury) is a syndrome characterized by a
sudden and usually reversible loss of renal function.
 It develops over days or weeks and it usually results in:
• Retention of nitrogenous compounds and other waste products.
• Sudden decline in GFR(hours to days)
• Disturbance in extracellular fluid volume
• Disturbance in electrolyte and acid base homeostasis
• Reduction in urine volume.
 There are >30 definitions used in published studies
INTRODUCTION

4. EPIDEMIOLOGY
 AKI complicates ~5-7% of hospital admissions worldwide and up to 30% of
admissions to the intensive care unit.
 The epidemiology of AKI differs greatly between developed and developing
countries owing to differences in demographics, economics, geography and co-
morbid disease burden.
 In Nigeria overall hospital prevalence is 3.07% with community acquired AKI at
2.23% and Hospital acquired AKI at 0.84%. Olowu et al, 2012.
 Anorchie et al reported a hospital prevalence of 11.7 cases/year, an incidence of
4.7% in Portharcourt, 6.6% in Zaria and 7.1% in Enugu.

5. CLASSIFICATION OF ACUTE KIDNEY INJURY
 The causes of AKI have traditionally been divided into three broad categories:
 PRE RENAL (HEMODYNAMIC) AKI
 INTRINSIC/INTRA-RENAL (PARENCHYMAL) AKI
 POST RENAL (OBSTRUCTIVE) AKI

6. A SUMMARY OF THE OF THE MAJOR CAUSES OF ACUTE KIDNEY INJURY

7. PRE RENAL (HEMODYNAMIC) AKI
 Pre renal AKI is the most common form of AKI and it represents a physiologic
response to mild-moderate hypoperfusion.
 Pre renal AKI is rapidly reversible upon restoration of renal blood flow and
glomerular ultrafiltration pressure.
 Although a more severe hypoperfusion may result in ischemic injury of the renal
parenchyma and intrinsic renal AKI
 Thus, both prerenal and intrinsic renal AKI due to ischemia are part of a spectrum
of manifestation of renal hypoperfusion

8. CAUSES OF PRERENAL AKI
Hypoperfusion Nephrotoxic Drugs/Drugs that cause
Impaired renal autoregulation
Hypovolemia (hemorrhage, burns,
dehydration, G.I fluid loss, osmotic diuresis)
Cyclosporine
Decreased cardiac output (diseases of
myocardium, valves)
ACE-I/ARB
Liver failure NSAIDs
Renal artery stenosis Chemotherapy
Sepsis Diuretics
Cardiogenic shock

9. PATHOPHYSIOLOGY
 The kidney can regulate its own blood flow and GFR over a wide range of perfusion
pressures.
 When the perfusion pressure falls the hypovolemia leads to glomerular
hypoperfusion, but filtration rate is preserved during mild hypoperfusion through
several compensatory mechanisms to make the resistance vessels in the kidney
dilate to facilitate flow.
 During states of severe hypoperfusion the compensatory responses are
overwhelmed and GFR falls leads to prerenal AKI

10. NSAIDS:- They reduce afferent renal vasodilation
ACEIs and ARBs:- limit renal efferent vasoconstriction

11. INTRINSIC/INTRA-RENAL (PARENCHYMAL) AKI
 Intrinsic AKI refers to disease processes which directly damage the kidney itself.
 It accounts for nearly 40% of all AKI
 In many cases, prerenal azotemia itself advances to tubular injury.
 It can be due to the damage of one or more of the kidney structures, including the
glomeruli, kidney tubules, or the interstitium.
 The most common causes of intrinsic AKI are: sepsis, ischemia and nephrotoxins.
 The most common way intrinsic renal AKI presents is as ATN

12. CAUSES
Major causes are:
 Sepsis-Associated AKI
 Ischemia-Associated AKI
 Nephrotoxin-Associated AKI

13. PATHOPHYSIOLOGY 1
Sepsis-Associated AKI
 Sepsis results in generalized arterial vasodilatation especially of the efferent
arteriole, this is mediated in part by cytokines early in the onset of sepsis. All these
leads to a reduction in GFR.
 It may also cause microvascular thrombosis by causing endothelial damage.
 It also causes activation of reactive O2 species which may injure renal tubular cells

14. PATHOPHYSIOLOGY 2
Ischemia-Associated AKI
 The kidneys are the site of one of the most hypoxic regions in the body, the renal medulla.
 Ischemia alone in a normal kidney is usually not sufficient to cause severe AKI.
 Clinically, AKI more commonly develops when ischemia occurs in the context of limited
renal reserve (e.g., chronic kidney disease or older age) or coexisting insults such as
sepsis, vasoactive or nephrotoxic drugs, rhabdomyolysis, or the systemic inflammatory
states associated with burns and pancreatitis.

16. PATHOPHYSIOLOGY 3
Nephrotoxin-Associated AKI
 The kidney is highly susceptible to nephrotoxicity due to extremely high blood
perfusion resulting in high-concentration exposure of toxins to tubular, interstitial,
and endothelial cells
 All structures of the kidney are vulnerable to toxic injury, including the tubules
(ATN), interstitium (AIN), vasculature, and collecting System.

18. ACUTE TUBULAR NECROSIS (ATN)
ATN Prerenal
Cr increases at 0.3-0.5
/day
increases slower than
0.3 /day
U Na, FeNa UNa>40
FeNa >2%
UNa<20
FeNa<1%
UA epi cells, granular
casts
Normal
Response to volume Cr won’t improve
much
Cr improves with IVF
BUN/Cr 10-15:1 >20:1

20. POST RENAL/OBSTRUCTIVE AKI
 Here, uremia results from obstruction of the urinary tract.
 May start at any point from the renal pelvis to the external urethral orifice
 Obstruction may be caused by functional or structural derangements anywhere
from the renal pelvis to the tip of the urethra.
 The block may be either partial or total.
 It's usually of insidious onset
 Normal urinary flow rate does not rule out the presence of partial obstruction

21. CAUSES
Mechanical causes Disease causes
Ureteric obstruction Strictures, litigation during
pelvic surgery
Retroperitoneal
(tumor/fibrosis),
urolithiasis,
Bladder neck obstruction Hemorrhage/clot BPH, prostatic CA, bladder
tumor
Urethral obstruction Obstructed Foley catheter,
stricture, bladder hematoma
Tumor, BPH, tumor, phimosis
Other causes include:
 Tubular obstruction from crystals
 Renal vein thrombosis
 Neurogenic bladder

22. PATHOPHYSIOLOGY
 The pathophysiology of postrenal AKI involves hemodynamic alterations triggered
by an abrupt increase in intratubular pressures.
 An initial period of hyperemia from afferent arteriolar dilation is followed by
intrarenal vasoconstriction.
 The vasoconstriction is from the generation of angiotensin II, thromboxane A2,
and vasopressin, and a reduction in NO production.
 Reduced GFR is due to under-perfusion of glomeruli and, possibly, changes in the
glomerular ultrafiltration coefficient.

23. CLINICAL FEATURES
Careful history is essential:
 History of exposure to nephrotoxic substances
 History of skin rashes: this may indicate allergic nephritis
 History of heart disease, liver disease, previous renal disease, kidney stones, BPH?
 History and/or evidence of volume depletion: diarrhoea, bleeding
 History and/or ischemia or trauma to the legs may indicate rhabdomyolysis
 Prostatic disease, nephrolithiasis
 History of any recent illnesses?
 History of recent surgical or radiological procedures
 Past and present medications
 Pelvic and per-rectal examination: to check for prostatic enlargement.
 Any edema, change in urination?

24. SIGNS AND SYMPTOMS OF AKI
Signs symptoms of AKI may include:
 Hyperkalemia
 Nausea/Vomiting
 HTN
 Pulmonary edema
 Ascites
 Asterixis
 Encephalopathy

25. DIAGNOSIS
Criteria for diagnosis:
 The presence of AKI is usually inferred by an elevation in the SCr concentration.
 AKI is currently defined by a rise from baseline of at least 0.3 mg/dL within 48 h or
at least 50% higher than baseline within 1 week, or a reduction in urine output to
less than 0.5 mL/kg per hour for longer than 6 h.
 The distinction between acute and CKD or even acute-on chronic kidney disease,
cannot be readily apparent in a patient presenting with uremia.
 In view of these difficulties, the Acute Dialysis Quality Initiative Group proposed
the RIFLE criteria

26. THE RIFLE CRITERIA
 The RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria indicate an
increasing degree of renal damage and have a predictive value for mortality.
 It utilizes either increases in serum creatinine(SCr) or decreases in urine output.
 It characterizes three levels of dysfunction (R, I, F) and two outcome measures (L, E).
STAGE GFR CRITERIA URINE OUTPUT (UO) CRITERIA
Risk SCr sed * 1.5 or GFR sed >25% UO <0.5mL/kg/h *6h
Injury SCr sed *2 or GFR sed >50% UO <0.5mL/kg/h *12h
Failure SCr sed * 3 or GFR sed >75% or
SCr >= 4mg/dL; acute rise >=0.5mg/dl
UO <0.3 mL/kg/h * 24h (oliguria) or
Anuria * 12
Loss Persistent AKI >4weeks High specificity
ESKD Complete loss of kidney function >3 months

27. INDICATIONS OF DIALYSIS IN ACUTE RENAL FAILURE (ARF)
• Severe fluid overload
• Refractory hypertension
• Uncontrollable hyperkalemia
• Nausea, vomiting, poor appetite, gastritis with hemorrhage
• Lethargy, malaise, somnolence, stupor, coma, delirium, asterixis, tremor, seizures,
• Pericarditis (risk of hemorrhage or tamponade)
• bleeding diathesis (epistaxis, gastrointestinal (GI) bleeding and etc.)
• Severe metabolic acidosis
• Blood urea nitrogen (BUN) > 70–100 mg/dl

28. DIALYSIS INDICATOR MNEMONIC
AEIOU:
• Acid-base problems
• Electrolyte problems
• Intoxications
• Overload, fluid
• Uremic symptoms

29. DIFFERENTIAL DIAGNOSIS
Differentials to consider in AKI includes the following
 Abdominal aneurysm
 Alcohol toxicity
 Alcoholic ketoacidosis
 Chronic renal failure
 Dehydration
 Gastrointestinal bleeding
 Heart failure
 Renal calculi
 Sickle cell anaemia
 Urinary obstruction
 Urinary tract infection

30. INVESTIGATION
This includes:
 Urine analysis:- Urine electrolytes(FeNa, FeUrea, Uric acid)Urine M/C/S, Urine
protein/Cr, Urine Eosinophilia(+ve in allergic nephritis)
 Hematological:- FBC, blood cultures, serologic(HBV, HCV, ANA, Anti-GbM antibody)
 Blood chemistry:- SCr, BUN Electrolytes
 Kidney biopsy
 Radiological imaging:- Renal USS(kidney size, renal calculi, renal VT)
FeNa = (urine Na x plasma Cr)
(plasma Na x urine Cr)
FeNa<1% FeNa 1%-2% FeNa >2%
Pre renal AKI Pre renal AKI, ATN or AIN ATN

31. COMPLICATIONS
 The kidney plays a central role in homeostatic control of volume status, blood pressure,
plasma electrolyte composition, and acid-base balance, and for excretion of nitrogenous
and other waste products.
 Thus any defect in its function may result in any of the following complications:
• Chronic renal failure
• Uremia
• Hypervolemia and Hypovolemia
• Hyponatremia (serum Na+ conc. <135 mEq/L)
• Hyperkalemia(serum K+ conc. > 5.5 mEq/L)
• Acidosis(pH <7.35
• Hyperphosphatemia(serum ph conc. >5.5mg/dl)
• Hypocalcemia(serum Ca+2 <8.5 mg/dl)
• Infections

32. TREATMENT OF AKI 1
The aims of treatment in AKI are:
 Early identification and correction of underlying cause
 Restoration of renal perfusion
 Limit injury
 Relieve obstruction if present
 Treat complication
 Diet
 Review medication

33. TREATMENT OF AKI 2
 The current treatment for AKI is mainly supportive in nature; as no therapeutic modalities
to date have shown efficacy in treating AKI.
 Treatment aims to identify & correct underlying causes of acute kidney injury and should
be done at the earliest indication of renal dysfunction.
 SCr doesn’t rise to abnormal levels until a large proportion of the renal mass is damaged
thus the rise of SCr may not be evident before 50% of the GFR is lost.
 Optimization of hemodynamics to increase renal perfusion
 Identify and aggressively treat infection (early removal of Foley catheters, and minimize
indwelling lines)

34. TREATMENT OF AKI: Treat complications
In the absence of dialysis, the most common causes of death are hyperkalemia and
pulmonary edema, followed by infection and uremia itself.
Initial management is targeted at these priorities.
 Correct fluid imbalances: strict I/O’s, daily wts. determine fluid balance goals daily, fluid
selection or diuresis, readjust for UOP recovery, post diuresis or dialysis
 Electrolyte imbalances (low K/phos diet, binder)
 Metabolic acidosis (Bicarb deficit, mode and rate of replacement)
 Nutrition: adjust TPN/protein intake
 Medication dosing: adjustment for eGFR to avoid under or over dosing, timing for
dialytic therapy, reassess dosing for renal recovery or dialysis modality)
 Procedural considerations (prefer non-contrast CT, appropriate to delay contrast
exposure, prophylaxis)

35. TREATMENT OF AKI 3
Minimizing nephrotoxic substances:
 Avoid or minimize use of Aminoglycosides, Amphotericin, Bactrim, Vancomycin, NSAIDs,
IV contrast, Fleet’s enemas
 Renal dose medications – especially antibiotics and monitor level
 Cautious use of (metformin, long acting oral hypoglycemic agents, insulin, gemfibrozil and
statins, neurotin, colchicine/allopurinol, morphine/codeine)

36. CLINICAL COURSE AND 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.
 Prerenal azotemia, with the exception of the cardiorenal and hepatorenal syndromes, and
postrenal azotemia carry a better prognosis than most cases of intrinsic AKI.
 In uncomplicated ARF, such as that due to simple hemorrhage or drugs, mortality is low
even when renal replacement therapy is required.
 In AKI associated with serious infection and multiorgan failure, mortality is 50–70%
 Outcome is usually determined by the severity of the underlying disorder and other
complications, rather than by renal failure itself.
 Patients with AKI are more likely to die prematurely after they leave the hospital even if
their kidney function has recovered.

37. BEST TREATMENT IS PREVENTION!
Be aware of pts who are at risk for AKI, they include:
 Volume depletion or Hypotension
 Sepsis
 Pre-existing renal, hepatic, or cardiac dz
 Diabetes mellitus
 Elderly
 Exposure to nephrotoxins
• Aminoglycosides, amphotericin, immunosuppressive agents, chemo., NSAIDs,,
RAAS blockers, intravenous contrast media
 Post cardiac or vascular Surgery pts or ICU pts with multiorgan failure

38. IN SUMMARY…
 AKI is increasingly common.
 It involves high cost of management, carries a high morbidity and mortality
risks.
 The most common cause of in-hospital AKI is ATN that results from multiple
acute insults (sepsis, ischemia, or nephrotoxin).
 No drug treatment has been shown to limit the progression of, or speed up
recovery from AKI.
 Review medications and adjust dose
 Recognize risk factors
 The Best Treatment is PREVENTION and avoid further renal damage!

39. THANK YOU