ACUTE KIDNEY INJURY

LAGOS | LAO | MENDOZA | NERA

INTRODUCTION
INTRODUCTION
A clinical syndrome generally defined by an abrupt
reduction in kidney function as evidenced by changes
in, serum creatinine (Scr), blood urea nitrogen (BUN),
and urine output.
It is also defined (KDIGO, March 2012) as any of the
following:
1. Increase in SCr by ⩾0.3mg/dl (⩾26.5µmol/l) within
48 hours
2. Increase in SCr to ⩾1.5 times baseline, which is
known or presumed to have occurred within the
prior 7 days
3. Urine volume <0.5ml/kg/h for 6 hours
EPIDEMIOLOGY
AKI is a global problem and occurs in the
community, in the hospital where it is common
on medical, surgical, pediatric, and oncology The burden of AKI may be
wards, and in ICUs. most significant in developing
countries with limited
AKI is more prevalent in (and a significant risk
resources for the care of these
factor for) patients with chronic kidney disease
patients once the disease
(CKD). Individuals with CKD are especially
progresses to kidney failure
susceptible to AKI which, in turn, may act as a
necessitating RRT.
promoter of progression of the underlying CKD.
ETIOLOGY
The causes of acute kidney injury can be divided
into three categories:
1. Prerenal (caused by decreased renal
perfusion, often because of volume
depletion)
2. Intrinsic renal (caused by a process within
the kidneys
3. Postrenal (caused by inadequate drainage
of urine distal to the kidneys)

In patients who already have underlying chronic

kidney disease, any of these factors, but
especially volume depletion, may cause acute
kidney injury in addition to the chronic
impairment of renal function.
ETIOLOGY
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY ➔
➔
Also known as prerenal azotemia
Results from the hypoperfusion of
the renal parenchyma
➔ Decreased filtration through the
PRE RENAL glomerulus, leading to an
“Before the kidney” elevation in the patient’s
creatinine and, if severe enough,
dysregulation of electrolyte and
fluid homeostasis.

CAUSES:
1. Hypovolemia
2. Impaired cardiac function
3. Systemic vasodilation
4. Increased vascular resistance
PATHOPHYSIOLOGY
- Haemorrhage
- GI losses (diarrhea, vomiting)
- Dehydration
- Renal fluid loss (over-diuresis)
- Third space (burns, peritonitis, muscle
Hypovolemia trauma)
PATHOPHYSIOLOGY - Congestive heart failure
- Acute myocardial infarction
- Massive pulmonary embolism
Impaired cardiac function

NORMAL

PRE RENAL AKI

PATHOPHYSIOLOGY COMPENSATORY MECHANISM
Decreased renal blood flow caused by:
Hypovolemia
Impaired cardiac output

Decreased glomerular filtration rate

Detection

RAAS Activation Afferent arteriole dilation

- Thirst (Increase Increased vasodilatory
blood volume) prostaglandins These homeostatic mechanisms are often able to maintain
- Renal sodium and arterial pressure and renal perfusion, potentially averting
fluid retention Efferent arteriole constriction the progression to AKI. If, however, the decreased renal
- Systemic Mediated by angiotensin II perfusion is severe or prolonged, these compensatory
vasoconstriction mechanisms may be overwhelmed, and prerenal AKI will be
clinically evident.
PATHOPHYSIOLOGY
- Antihypertensive medications (ACEi or ARB)
- Cirrhosis
- Anaphylaxis
- Sepsis
Systemic vasodilation
PATHOPHYSIOLOGY -
-
Hepatorenal syndrome
Drugs that cause renal vasoconstriction
(i.e. cyclosporine, NSAID medications,
Aminoglycosides, Amphotericin B)

Increased vascular resistance

PATHOPHYSIOLOGY
INTRINSIC ➔ Results from the direct damage to
the kidney and categorized on the
“The kidney itself”
basis of injured structures.
CAUSES:
1. Vascular damage
2. Glomerular damage
3. Tubular damage
4. Interstitial damage
PATHOPHYSIOLOGY VASCULAR DAMAGE

➔ Large vessels
- (bilateral renal artery stenosis, bilateral
renal vein thrombosis)
➔ Small vessels
- (vasculitis, malignant hypertension,
atherosclerotic or thrombotic emboli,
haemolytic uraemic syndrome,
thrombotic thrombocytopenic
purpura)
PATHOPHYSIOLOGY GLOMERULAR DAMAGE

➔ Acute glomerulonephritis
- The glomerulus is one of two capillary
beds in the kidney. It serves to filter fluid
and solute into the tubules while
retaining proteins and other large blood
components in the intravascular space.
- Inflammation of the glomeruli and
subsequent damage of the glomeruli
leading to hematuria, proteinuria, and
azotemia; it may be caused by primary
renal disease or systemic conditions.
PATHOPHYSIOLOGY TUBULAR DAMAGE

- Acute tubular necrosis

➔ Renal ischaemia (shock,
complications of surgery,
haemorrhage, trauma, bacteraemia,
pancreatitis, pregnancy)
➔ Nephrotoxic drugs (antibiotics,
antineoplastic drugs, contrast media,
organic solvents, anaesthetic drugs,
heavy metals)
➔ Endogenous toxins (myoglobin,
haemoglobin, uric acid)
PATHOPHYSIOLOGY INTERSTITIAL DAMAGE

- Acute interstitial nephritis

- An idiosyncratic delayed
hypersensitivity immune reaction that
is most commonly caused by:
➔ Infections (bacterial, viral)
➔ Medications (antibiotics, diuretics,
NSAIDs, and many more drugs)
PATHOPHYSIOLOGY
POST RENAL - The result of obstruction at any level
“After the kidney” within the urinary collection system.
- If the obstructing process is above
the bladder, it must involve both
kidneys (one kidney in a patient with a
single functioning kidney) to cause
clinically significant AKI, as one
functioning kidney can generally
maintain a near-normal GFR.
 PATHOPHYSIOLOGY
BLADDER OUTLET OBSTRUCTION
BPH, Malignancy, Anticholinergic drugs, displaced
bladder catheter

URETERAL OBSTRUCTION
Malignancy, retroperitoneal fibrosis, nephrolithiasis

RENAL PELVIS/TUBULAR OBSTRUCTION

Nephrolithiasis, drugs
CLINICAL PRESENTATION AND
DIAGNOSIS
CLINICAL PRESENTATION

AKI is one of a number of conditions that affect kidney

structure & function.

The syndrome encompasses various etiologies:

● Specific kidney diseases

● Non-specific conditions
● Extrarenal pathologies
 Mild to moderate AKI: may be asymptomatic

PRESENTATION Severe/prolonged untreated AKI:

● Anemia
○ Fatigue
● Hypovolemia
○ Sepsis
○ Dec. urine output
○ Syncope
● Hypoalbuminemia
○ Generalized edema
● Electrolyte imbalance
○ Muscle weakness
○ N/V
● Uremic encephalopathy
○ Decline in mental state
○ Asterixis
DIAGNOSIS

Any of the following:

● Increase in SCr by >0.3 mg/dL w/in 48 hours;

● Increase in SCr to >1.5x baseline w/in past 7 days;
● Urine output <0.5 mL/kg/hr for 6 hours
STAGING
RIFLE
Criteria
COMPARISON
PHARMACOLOGICAL THERAPY AND
TREATMENT
General Approach

- Ameliorating any identifiable underlying causes of AKI

- Avoid nephrotoxic medications
- Supportive care on managing fluid overload and
electrolyte imbalances
 HYDRATION
Isotonic Saline (0.9% Sodium Chloride)
- STANDARD CHOICE
- Down-side of Hyperchloremia
Tx: Sodium bicarbonate 1-6g/day in divided doses
Albumin
- Rescuscitative agent
- Hypoalbuminemia patients who are resistant to crystalloid therapy
Hydroxyethylstarch (HES)
- Alternative for albumin
- Generally avoided for patients at risk of AKI
ELECTROLYTE MANAGEMENT
HYPERKALEMIA
● Dialysis
● Calcium Chloride/Calcium Gluconate 10%
● Sodium Bicarbonate 8.4%
● Regular Insulin
● Sodium polystyrene sulfonate (SPS) HYPOCALCEMIA
HYPERPHOSPATEMIA ● IV: Calcium Gluconate 10%
● Calcium Gluconate 10% ● Oral: Calcium Carbonate
● Oral Calcium salts
● Sevelamer
● Dialysis
● Aluminum Hydroxide
NUTRITIONAL CONSIDERATIONS
Nutritional management of critically ill
patients with AKI can be extremely
complex, as it needs to account for
metabolic derangements resulting from
both renal dysfunction and underlying
disease processes, as well as the
effects of RRT on nutrient balance.
Stress, inflammation, and injury lead to
hypermetabolic/hypercatabolic states
and may alter the nutritional
requirements.
The KDIGO guidelines currently recommend a
caloric intake goal of 20 to 30 kcal/kg/day
(84-126 kJ/kg/day); irrespective of the stage of
renal impairment and preferentially through the
enteral route.
In the setting of noncatabolic AKI without need
for dialysis, 0.8 to 1 g/kg/day of protein is
suggested and 1 to 1.5 g/kg/day if patient is
receiving RRT.
CRRT is associated with an increased removal of
small water-soluble molecules such as amino
acids and certain nutrients. As a result,
hypercatabolic patients receiving CRRT will
typically have higher protein requirements up to a
maximum of 1.7 g/kg/day.
GLYCEMIC CONTROL
Glycemic control in critically ill patients is
important as stress hyperglycemia and
insulin resistance are common during
critical illness and are associated with
increased mortality. The causes of
insulin resistance are multifactorial but
include impaired glucose homeostasis
due to loss of the kidney’s metabolic
function, and decreased hepatic and
peripheral glucose uptake secondary
to uremia.
Current KDIGO guidelines suggest using
insulin therapy to target plasma glucose
of 110 to 149 mg/dL (6.1-8.3 mmol/L).
Other guidelines such as the American
Diabetes Association and the American
Society of Parenteral and Enteral
Nutrition have recommended a glycemic
target range of 140 to 180 mg/dL
(7.8-10.0 mmol/L) in critically ill patients.
DIURETICS
LOOP DIURETICS
Drug MOA Pharmacokinetics Drug - drug Side effects Latest CPG
interactions

Furosemide It acts at the luminal Onset: Diuresis: 30 - 60 min Pregnancy Electrolyte the KDIGO guidelines
(Lasix) surface of the thick (PO), 30 min (IM) catergory: C disturbances, recommend limiting the use of
ascending limb of the Duration: 6-8hr ( oral), 2 hr Dehydration, loop diuretics to the
loop of Henle and (IV) Severe Hypovolemia, management of fluid overload
inhibit the Na-K-2Cl Absorption: Fairly rapidly hypotension and Hyponatremia, and avoiding their use for the
cotransporter, resulting absrobed from the GI tract. deterioraiton in Hypokalemia, sole purpose of prevention or
in a loss of the high Bioavailability: Approx. renal function Hypochloremia treatment of AKI.
medullary osmolality 60-70% with ACE
and decreased ability to Distribution: Crosses the inhibitors or
reabsorb water placenta, enters breast milk. ARBs
Plasma protein binding: 99%
ROA: PO, IV (mainly albumin) Reduced effect
Metabolism: undergoes with and
minimal hepatic metabolism decreased renal
Excretion: Mainly via urine elimination of
(as unchanged drug). probenacid,
methotrexate
VASODILATOR THERAPY

Drug MOA Pharmacokinetics Drug - drug Side effects Latest CPG

interactions

Dopamine At low doses, it Onset: <5 min. Pregnancy Ectopic Once commonly used to
(low-dose) preferentially Duration: <10 min. category: C heartbeats, prevent & protect patients from
stimulates D1 and D2 angina, brady/ developing AKI, it has been
receptors in the renal Absorption: Inactivated when Arrhythmias tachycardia, abandoned in clinical practice
vasculature, which given orally. when used palpitations, due to multiple negative
leads to vasodilation Metabolism: Metabolised in together with hypotension/ studies.
and promotes renal the liver, kidney and plasma cyclopropane & HTN,
blood flow to preserve by MAO and COMT to inactive halogenated HC vasoconstrictio
glomerular filtration. compounds homovanillic anesthesia n, dyspnea,
acid and N/V, , azotemia,
ROA: IV 3,4-dihydroxyphenylacetic Antagonized by anxiety,
acid. beta-blockers. piloerection
Excretion: Via urine as
metabolites. Elimination Hypotension & Potentially
half-life: Approx 2 min. bradycardia w/ fatal:
phenytoin. ventricular
arrhythmias
(rare)
VASODILATOR THERAPY

Drug MOA Pharmacokinetics Drug - drug Side effects Latest CPG

interactions

Fenoldopam A pure dopamine type-1 Onset: 4 mins Pregnancy Headache, The guideline recommendation
mesylate receptor agonist that Duration: <10 min. category: B flushing, against using fenoldopam
(Corlopam) has similar nausea, places a high value on avoiding
hemodynamic renal Absorption: Inactivated when Hypotension & hypotension, potential hypotension and harm
effects as low-dose given orally. reflex tachycardia reflex associated with the use of this
dopamine, without Metabolism: hepatic (not when taken w/ tachycardia, vasodilator in high-risk
systemic a-or CYP450) beta-blockers. and increased perioperative and ICU patients,
b-adrenergic Excretion: 90% renal, 10% intraocular and a low value on potential
stimulation. fecal. Half-life: 5 mins pressure benefit, which is currently only
suggested by relatively low-
ROA: IV Serious, rare: quality single-center trials.
Allergic
reaction,
anaphylaxis
GROWTH FACTOR INTERVENTION

● (rh)IGF-1 is NOT recommended to treat or prevent AKI.

○ No cost benefit, and potential harm (dec. GFR)

● Erythropoietin
○ Animal studies show promise, as it consistently improved functional recovery.
○ The renoprotective action of erythropoietin may be related to pleomorphic properties including
antiapoptotic and antioxidative effects, stimulation of cell proliferation, and stem-cell
mobilization.
○ One RCT in humans was negative, but usefulness should further be tested.
NON PHARMACOLOGICAL THERAPY
AND TREATMENT
RENAL REPLACEMENT THERAPY
- It is used to treat fluid overload, electrolyte and acid-base imbalances resulting
from severe AKI.

Indications Clinical Setting

Indications for RRT

A - Acid-Base Abnormalities Metabolic acidosis (pH <7.2)

E - Electrolyte imbalance Severe hyperkalemia, hypermagnesemia

I - Intoxication Salicylate, lithium, methanol, ethylene glycol,

theophylline

O - Fluid Overload Pulmonary edema & unresponsive to diuretics

U - Uremia Uremia or associated complication (neuropathy,

encephalopathy, pericarditis)
Intermittent Hemodialysis

- Delivered 3 to 6 times a week, 3 to 4 hours

per session, with a blood flow rate of over
250 mL/min and a dialysate flow rate of
500 to 800 mL/min
CONTINUOUS RENAL REPLACEMENT THERAPY
- Performed continuously (24 hours per day)
with a typical blood flow of 100 to 300
mL/min and a dialysate flow of 17 to 40
mL/min if a diffusive CRRT modality is
used
- Variants:
1. Continuous venovenous
hemofiltration (CVVH)
2. Continuous venovenous
hemodialysis (CVVHD)
3. Continuous venovenous
hemodiafiltration (CVVHDF)
 Hybrid Dialysis Therapies

- Known as sustained low-efficiency dialysis (SLED) and slow extended daily

dialysis
- These therapies use lower blood (150-200 mL/min) and dialysate (300-400
mL/min) flow rates with extended treatment periods of 6 to 12 hours
- Anticoagulation is still required, but the amount necessary compared with CRRT is
lower
Peritonial Dialysis

- Peritoneum is used as semi-permeable membrane for diffuse removal of

solutes
- Direct comparative effectiveness trials are extremely limited.
- Indications for PD: bleeding diathesis, hemodynamic instability and difficulty
in obtaining a vascular access.
- Contraindications: Extremely high catabolism, severe respiratory failure,
severe ileus, intra-abdominal hypertension, recent abdominal surgery and
diaphragmatic peritoneum-pleura connections
Supportive Therapy

- Adequate nutrition
- Correction of electrolyte and acid-base abnormalities (hyperkalemia and
metabolic acidosis)
- Fluid management
- Correction of any hematologic abnormalities
CLINICAL PRACTICE GUIDELINES
RATIONALE

- AKI is common.
- AKI imposes a heavy burden of illness (morbidity
and mortality).
- The cost per person of managing AKI is high.
- AKI is amenable to early detection and potential
prevention.
- There is considerable variability in practice to prevent,
diagnose, treat, and achieve outcomes of AKI.
- CPGs in the field have the potential to reduce variations,
improve outcomes, and reduce costs.
- Formal guidelines do not exist on this topic.
RECOMMENDATIONS

● Risk stratification &

management according to
susceptibilities & exposures
● Daily SCr for high-risk pts.

Note:

● 30% of AKI pts still have inc.

risk of CKD, CVD, and death
even after recovery
 ● Do not use: diuretics,
low-dose dopamine, ANP,

Prevention & rhIGF-1, NAC *

● Avoid nephrotoxic drugs:

Treatment aminoglycosides,
conventional amphotericin
B **
Dos & Donts
● Do use isotonic solutions:
crystalloids, contrast
media, NaCl, NaHCO3
 1. Determine the cause
2. Monitor SCr & U/O to stage
3. Manage based on #1 & 2

Treatment Goals
4.
Reduce kidney injury &
complications related to
dec. kidney f(x)
Follow-up 3 months after
a. (+) CKD = follow CKD
guidelines
b. (-) CKD = consider pt
inc. risk; follow CKD
Guideline 3
EVALUATION OF AKI according to stage & cause (fig. 5)
Continue monitoring, No
if high-risk AKI
AIN
Yes

GN Ischemic
Hx & PE

Fluid depletion Thrombotic

Toxic
Clinical tests microangiopathy
Obstruction
Heart Renal
insufficiency Inflammation
Lab values (+) microangiopathy

Renal
Ultrasound Myeloma Others
vasoconstriction AKI stage
Yes Yes Yes

Yes No No No
Dec. kidney Obstruction
Specific Diagnosis Nonspecific AKI
perfusion? suspected?
UPDATED JOURNALS
 Improved long-term survival with home hemodialysis compared with
institutional hemodialysis and peritoneal dialysis: a matched cohort study
Helena Rydell , Kerstin Ivarsson, Martin Almquist, Mårten Segelmark and Naomi Clyne

Background
Survival for patients on dialysis is poor, despite improvement over time both in the US and in
Europe. The aim of the present study is to analyse the long-term effects of HHD on patient
survival and on subsequent renal transplantation, compared with institutional hemodialysis
(IHD) and peritoneal dialysis (PD), taking age and comorbidity into account.
Methods
Patients starting HHD as initial renal replacement therapy (RRT) were matched
with patients on IHD or PD, according to gender, age, Charlson Comorbidity Index
and start date of RRT, using the Swedish Renal Registry from 1991 to 2012.
Survival analyses were performed as intention-to-treat (disregarding changes in
RRT) and per-protocol (as on initial RRT).
Conclusion
This study showed a significant long-term survival advantage for patients starting
HHD as initial RRT compared with IHD and PD. Subsequent renal transplantation
was more common among patients starting HHD, but there was no difference in
subsequent renal graft survival between HHD and IHD or PD as initial RRT. In most
countries, patients treated with HHD still comprise less than 5% of the entire
dialysis population. The results of this study should encourage increased use of
HHD in order to improve the long-term prognosis for dialysis patients.
Association Between a Chloride Liberal vs Chloride-Restrictive Intravenous
Fluid Administration Strategy and Kidney Injury in Critically Ill Adults
Yunos, M., Bellomo, R., Hegarty, C., Story, D., Ho, L., Bailey, M.

Background
The administration of IV Chloride is ubiquitous in critical care medicine. The
aim of this study is to assess the association of a chloride-restrictive (vs
chloride-liberal) intravenous fluid strategy with AKI in critically ill patients.
Method
Patients were admitted consecutively over 6 months. First set is the control
period where the patients were given IV fluids with that are chloride-rich
(Isotonic saline, Gelofusine, and 4% Albumin in sodium chloride). Second set is
the phase-out period that included education and preparation of all ICU staff and
logistic arrangements for fluid accountability and delivery. Third set is the
intervention period in which chloride-rich solutions were made available only
after prescription by the attending physician for specific conditions.

Conclusion
It was found that restricting intravenous chloride intake was associated with a
significant decrease in the incidence of AKI and the use of RRT.