Acute Kidney Injury -
Acute Renal Failure
Dr. Hossam Sherif, MD
Associate Professor of Internal Medicine
The term ‘Renal Failure’ means failure of renal
excretory function; filtration, reabsorption or
secretion.
This is accompanied to a variable extent by failure
of:
- Erythropoietin activation,
- Vitamin D hydroxylation (1,25 dihydroxycholecalciferol),
- Regulation of acid–base balance (plasma proteins,
phosphate, and bicarbonate and carbonic acid buffers), and
- Regulation of salt and water balance (aldosterone and
ADH hormones) and blood pressure (RAS system).
DEFINITION
Acute kidney injury has variably been defined as an
abrupt deterioration in parenchymal renal function,
which is usually, but not invariably, “reversible” over a
period of days or weeks.
Renal failure results in reduced excretion of
nitrogenous waste products, of which urea is the most
commonly measured.
A raised serum urea concentration (uremia, or
azotemia) is classified as:
(i) pre-renal, (ii) renal or (iii) post-renal.
ETIOLOGY OF ACUTE RENAL FAILURE
• PRE-RENAL 55-60%
• RENAL 35-40%
• POST-RENAL <5%
Acute Kidney Injury
• More than 35 definitions exist in literature
• Based on:
– Serum creatinine,
– Urine output, BUN,
– Renal replacement therapy
Acute Renal Failure
classification by urine volume
NON-OLIGURIC: > 500 ml/24 Hrs
OLIGURIC: < 400 ml/ 24 Hrs
ANURIC < 50 ml/24 Hrs
RIFLE Criteria
AKIN Diagnostic Criteria
• Requires 2 SCr values within 48 hours
• AKIN Stage 1-3 correlates with RIFLE risk,
injury, and failure
KDIGO Clinical Practice Guideline for Acute Kidney Injury.
International Society of Nephrology, 2012
Incidence of
Acute Kidney Injury
• Approximately 7% of all hospitalized patients
• 65-70% of critically ill patients
– RIFLE Stage F 10-20% of ICU admissions
– 45% developed AKI after ICU admission
• AKI requiring RRT: Mortality range 50-70%
• Sepsis most common cause
Risk Factors
• Nephrotoxic medications
• Radiographic contrast agents
• Gadolinium
• Trauma: Age > 60,
Multiple transfusions,
GCS < 10
Causes of AKI
Top 5 Other common causes
• Sepsis • Cardiopulmonary
• Major surgery bypass
• Low cardiac output • ACS
• Hypovolemia • Trauma
• Medications • Rhabdomyolysis
• GIT obstruction
Prevention
Primary prevention best, often unpredictable
• Contrast-induced nephropathy
– Give fluid, low volume non-ionic or isoionic
contrast agent
• Albumin after large-volume paracentesis may
decrease incidence of AKI
Secondary Prevention
• Recognize underlying risk factors
• Maintain renal perfusion
• Avoid hyperglycemia
• Avoid nephrotoxins
Pre-renal Disorders
• Represents 50% of acute oliguric renal failure
• UNa < 20 mEq/L, FENa < 1%
• Predisposed by:
1.Hypovolemia
2.Severe cardiac dysfunction
3.Loss of vascular tone
4.Renal vasoconstriction agents (NSAIDs)
5.Reduction in GFP (ACE-inhibitors)
Renal Disorders
• Impaired glomerular filtration, renal tubular
dysfunction, or both
• UNa > 40 mEq/L, FENa > 2%
• Described as 3 entities:
– Acute glomerulonephritis
– Acute tubular necrosis (most common)
– Acute interstitial nephritis
ACUTE RENAL FAILURE
• VASCULAR DISEASE
– VASCULITIS (SLE)
– SCLERODERMA
– THROMBOEMBOLIC DISEASE
– MALIGNANT HYPERTENSION
ACUTE RENAL FAILURE
• GLOMERULAR DISEASE
– ACUTE GLOMERULONEPHRITIS
• POST INFECTIOUS GN
• CRESCENTIC GN
– ANCA POSITIVE DISEASES
• GOODPASTURE’S DIS.
– ANTI- GLOMERULAR BASEMENT ANTIBODY
ACUTE INTERSTITIAL NEPHRITIS
(DRUG INDUCED)
• PENICILLINS • NSAID (FENOPROFEN)
• SULFONAMIDES • ALLOPURINOL
• CEPHALOSPORIN • PHENYTOIN
• RIFAMPIN ( 2ND TIME) • THIAZIDES
• QUINOLONES • FUROSEMIDE
• CIMETIDINE
Acute Interstitial Nephritis
• Fever
• Rash
• Eosinophilia
• Pyuria
• WBC Casts
Acute Tubular Necrosis
• Phases:
1 - Intra-renal micro-vascular vaso-constriction
2 - Tubular cell injury
3 - Tubular cellular recovery
• Ischemia and inflammatory cell injury
• Slough of tubular epithelial cells into lumen
• Obstructed proximal tubule creates back-pressure decreases
filtration
• Tubules and adjacent parenchyma involved
ACUTE RENAL FAILURE
• ACUTE TUBULAR NECROSIS
– ISCHEMIC INJURY
– TOXIC INJURY
• ENDOGENOUS TOXINS
– HEMOGLOBINURIA
– MYOBLOBINURIA (RHABDOMYOLYSIS)
– ENDOTOXEMIA
ACUTE RENAL FAILURE
• ACUTE TUBULAR NECROSIS
– EXOGENOUS TOXINS
• AMINOGLYCOSIDES
• RADIOGRAPHIC CONTRAST
• HEAVY METAL COMPOUNDS
• ETHYLENE GLYCOL
• METHANOL
• CARBON TETRACHLORIDE
Clinical Picture
• Rapidly progressive uraemia; anorexia, nausea,
vomiting and pruritus, followed by intellectual
clouding, fits, coma and haemorrhagic episodes.
Epistaxes and gastrointestinal haemorrhage
• Hyperkalaemia is common,
• Metabolic acidosis
• Hyponatraemia
• Pulmonary oedema
• Hypocalcaemia
Serum Creatinine
• Standard surrogate measure of GFR
• Affected by non-renal factors common in the
ICU (variable secretion, volumes of
distribution)
• Late marker of AKI
– Rise in SCr = ~ 50% loss of function
Biomarkers of acute kidney injury (AKI) include:
- Neutrophil gelatinase-associated lipocalin (NGAL)
- Interleukin-18 (IL-18)
- Kidney injury molecule-1 (KIM-1)
- Liver-type fatty acid–binding protein (L-FABP)
- Insulin-like growth factor-binding protein 7 (IGFBP7)
- Tissue inhibitor of metalloproteinases-2 (TIMP-2)
Renal Ultrasound
• Confirm number of kidneys
• Rule out obstruction
• Evaluate degree of chronicity if baseline lab
values are unknown
• Measure degree of volume depletion (IVC)
Urine Microscopy
• Urine Microscopy
– Examination of sediment, easy, cost-effective
• Abundant tubular epithelial cells (ATN)
• White cell casts (interstitial nephritis)
• Pigmented casts (myoglobinuria)
If unrevealing, urinary sodium determination
may be helpful
Urine Sodium
• In the setting of oliguria, urine sodium below
20 mEq/L usually indicates a prerenal disorder
• Elevated urine sodium can occur when a
prerenal disorder is superimposed on intrinsic
renal dysfunction (or diuretic therapy)
One of the most reliable parameters to determine
difference: FENa
FENa
• FENa < 1% = Prerenal disorder
• FENa > 2% = Intrinsic renal disorder
Management
Optimize Central Hemodynamics
• CVP 6-8 mmHg
• CO low? Push CVP 10-12 mmHg
• Still low? Cardiac contractility measurement
• Consider inotropic support agent
– Dopamine 5 mcg/kg/min
– Dobutamine 5 mcg/kg/min
– Goal CI above 3 L/min/m2
Avoid Fluid Overload
• Association with positive fluid balance and
increasing mortality
• Mean fluid balance differed between survivors
and non-survivors
• Patients requiring RRT, increase in fluid
balance 64.6% vs. 44.8% mortality
Maintain Perfusion
• To prevent injury, especially with compromised
autoregulation
• Volume
• Inotropic or vasopressor support
• Target MAP ≥ 65 mmHg generally accepted
Improving Perfusion
If oliguria persists despite adequate filling
pressure and flow…
• No evidence to support low-dose dopamine
Diuretics in AKI
• No findings to support
– Shortened duration of AKI
– Reduced need for RRT
– Improved outcomes
• Furosemide
– Less than 10% of bolus dose reaches tubule lumen
– Continuous infusion may be preferred method of
delivery, 1-9 mg/hr rates reported
Hyperkalemia
• Significance of urine output
• Role of increased catabolism or tissue
breakdown
• Factors affecting shift of Potassium out of cells
• Etiololgy of the renal failure
Hyperkalemia
• Never occurs in the absence of renal excretory
problem
- Peaked T-wave
- Flat P-wave
- Sine wave
Hyperglycemia
• Decreased incidence of AKI and requirement
for RRT with tight glucose control
Nutrition
• Malnutrition associated with increased
mortality
• AKI patients are hypercatabolic
• Consensus recommendation: 20-30
kcal/kg/day and 1.5 gm/kg/day protein
Renal replacement therapy (RRT):
Is the therapy that replaces the
normal blood-filtering function of
the kidneys.
RRT includes:
- Dialysis (hemodialysis or peritneal dialysis),
- Hemofiltration, and
- Hemodiafiltration
Also includes kidney transplantation, which is
the ultimate form of RRT.
Renal Replacement Therapy
• CRRT Continuous renal replacement therapy
• SCUF Slow continuous ultrafiltration
• CVVH Continuous venovenous hemofiltration
• CVVHD Continuous venovenous hemodialysis
Haemodialysis removes solutes by diffusion.
As such, it is relatively inefficient for solutes
of high molecular weight as clearance by
diffusion is inversely related to the molecular
weight of the solute.
Haemofiltration removes solutes by
convection. As such, efficiency remains more
constant for all solutes able to cross the semi-
permeable membrane.
Solute Clearance - Diffusion
• Small (< 500d) molecules
cleared efficiently
• Concentration gradient
critical
• Gradient achieved by
countercurrent flow
• Principal clearance mode
of dialysis techniques
Solute Clearance – Ultrafiltration & Convection
(Haemofiltration)
• Water movement “drags” solute
across membrane
• At high UF rates (> 1L/hour) enough
solute is dragged to produce
significant clearance
• Convective clearance dehydrates the
blood passing through the filter
• If filtration fraction > 30% there is
high risk of filter clotting*
• Also clears larger molecular weight
substances (e.g. B12, TNF, inulin)
* In post-dilution haemofiltration
Classic Indications for RRT
• A—acidosis
• E—electrolyte disturbances
• I —intoxication
• O—overload
• U—uremia
INDICATIONS FOR DIALYSIS IN ACUTE
RENAL FAILURE
UREMIC SYMPTOMS
~ nausea
~ neurologic
SEVERE FLUID OVERLOAD
REFRACTORY ELECTROLYTE DISORDERS
~hyperkalemia
SEVERE REFRACTORY ACIDOSIS
INDICATIONS FOR DIALYSIS IN ACUTE
RENAL FAILURE
• PERICARDITIS
• NEUROPATHY
• MENTAL STATUS CHANGE
• SEIZURES
• BLEEDING
• TOXINS----ETHYLENE GLYCOL, METHANOL
• PROPHYLACTIC
~recent studies fail to document benefit
Criteria for Initiation
• Severe acidemia (pH < 7)
• Hyperkalemia
• Pulmonary edema
• Severe dysnatremia
• Pericarditis
• Uremia encephalopathy
• Overdose with dialyzable drug
Therapeutic Goal Hemodynamics Preferred Therapy
Fluid removal Stable Intermittent UF
Unstable SCUF
Urea clearance Stable Intermittent HD
Unstable CRRT
Hyperkalemia Stable Intermittent HD
Unstable Intermittent HD
Metabolic acidosis Stable Intermittent HD
Unstable CRRT
Cerebral edema Stable CRRT
Unstable CRRT
Intermittent vs. Continuous
• Conflicting outcome data
• Recent meta-analysis demonstrated no
difference in mortality
• What about renal recovery?
– 2 studies—CRRT improved recovery
– 4 studies—No difference
– No definitive data
Continuous RRT
• Approximates “normal physiology”
– Slow correction of metabolic disturbances
– Volume removal better tolerated
• Goals
– Maintain fluid, electrolyte balance, acid/base,
prevent further renal damage, provide renal
support pending recovery
Discontinuation of CRRT
• No consensus in nephrology or critical care
literature
• UOP most important predictor of successful
discontinuation
– Greater than 400 mL/24 hrs without diuretics or >
2300 mL/24 hrs with diuretics, ≥ 80% chance of
success
Summary
• AKI is a common, complex condition
• Etiology often multifactorial
• Can be functional or structural
• “Acute kidney injury” replaces “acute renal
failure”
• Small changes in SCr associated with adverse
outcomes
– Short and long-term increase in morbidity and
mortality
Surviving Sepsis Campaign: International Guidelines
for Management of Sepsis and Septic Shock: 2016
Renal Replacement Therapy
Rhodes A. Intensive Care Med, 2017
Summary
• Diagnosis frequently delayed
• SCr poor marker of function in critically ill
• AKI increases risk of CKD
• AKI accelerates progression from CKD to ESRD
• Volume overload is associated with worse
outcomes
Good Luck
