Acute Kidney Injury

Renal physiology

 Kidney receives 20-30% of cardiac output

 Autoregulation
 BP is not good indicator
 Renal medulla – prone for hypoxemia as oxygen
consumption is high
Neonatal renal physiology

Renal blood flow-

 2.5 -4 % of CO at birth  6% at 24 hrs  10% at 1 week  15- 18 % at
6 wks
 increased renal perfusion pressure, increased systemic arteriolar
resistance, and decreased renal vascular resistance due to neuro humoral
changes with angiotensin II and prostaglandins

GFR
 Term- 20ml/min/m2  30- 40 ml/min/ m2 by 2 weeks  adult range by 2
yrs of age

Tubular reabsorption
 Immature in preterm infants
AKI- Definition

 Sudden deterioration in renal function

 results in the inability of the kidneys to maintain fluid and
electrolyte homeostasis
Diagnostic Criteria

 With in 48 hrs
50 % or greater increase in s.creatinine

{OR}

Oliguria for >6 hours

[< 0.5 ml/kg/ hr or < 1ml/kg/hr in a neonate ]

Incidence
 2-3% pediatric age group
 30-40% of PICU admissions
 8% of infants in neonatal intensive care units
 RIFLE and AKIN Criteria
RIFLE stage S creatinine Urine output AKIN stage
RISK s. Creatinine ᵡ 1.5 < 0.5 ml/kg/hr × 6 hrs 1
INJURY s. Creatinine ᵡ 2 < 0.5 ml/kg/hr × 12 hrs 2

FAILURE s. Creatinine ᵡ 3 (or) < 0.3 ml/kg/hr for 24 3

s. cr >4mg/dl with an hours (or)
acute raise of >_ 0.5 Anuria for 12 hrs
mg/dl

LOSS persistent renal

failure for >4 weeks
END STAGE persistent renal
RENAL failure for >3months
DISEASE
 Schwartz formula –
k× height (cms)
pRIFLE (2007) s.Cratinine (mg/dl)

k- 0.34 – preterm
0.45- term
0.55 – children and adolescent girls
0.7 – adolescent boys

pRIFLE criteria Estimated CrCl Urine out put

Early R Decrease by 25% < 0.5 ml/kg/hr × 8 hrs
I Decrease by 50% < 0.5 ml/kg/hr × 16 hrs
F Decrease by 75% (or) < 0.5 ml/kg/hr × 24 hrs
<35 ml/min/m2 (or) Anuria for 12 hrs

Late L persistent renal failure for

>4 weeks
E persistent renal failure for
>3months
 Neonatal - Kidney Diseases: Improving Global Outcomes
(KDIGO)

Stage Serum creatinine Urine output

0 No change in SCr or rise <0.3mg/dL >/= 0.5ml/kg/hr

1 SCr rise >/= 0.3mg/dL within 48hrs or <0.5ml/kg/hr for 6-12hrs

SCr rise >/=1.5-1.9 x reference SCr

2 SCr rise >/= 2-2.9 x reference SCr <0.5ml/kg/hr for >/= 12hrs

3 SCr rise >/=3 x reference SCr or <0.3ml/kg/hr for >/= 24hrs

SCr>/= 2.5mg/dl or receipt of dialysis or anuria for >/=12hrs
Risk factors for neonatal AKI

 Preterm
 VLBW and ELBW
 Sepsis
 Asphyxia undergoing therapeutic hypothermia
 ECMO
 CDH
 Neonatal surgeries
 Nephrotoxic medication
Etiology
PRERENAL - MC -40%
Intravascular volume depletion
• Dehydration
• Hemorrhage
• Burns
• Diuretics
Redistribution of fluids
• Sepsis
• Pancreatitis
• Intestinal obstruction
• Nephrotic syndrome
• Hepatic failure
Decreased cardiac output
• CCF
• Cardiogenic shock
• Myocarditis
• Cardiac tamponade
Drugs –
• NSAIDS
• ACE inhibitors
Pathophysiology

Prerenal AKI
 diminished effective circulating arterial volume ---
Inadequate renal perfusion --- decreased GFR

 Evidence of kidney damage is absent

 underlying cause of the renal hypoperfusion is reversed renal

function returns to normal
 hypoperfusion is sustained, intrinsic renal parenchymal
damage develops
 Intrinsic renal
Glomerulonephritis Endogenous toxins
 Postinfectious /  Rhabdomyolysis
poststreptococcal  Tumor lysis syndrome
 SLE Exogenous toxins
 HSP  Drugs –
 Membrano proliferative  Snake bite other
 Good pasture syndrome envenomation
 Radio contrast agents
Acute tubular necrosis  Chemicals- organic
Acute interstitial nephritis solvents , heavy metals,
insecticides
Vascular Infections –
 Malaria
 HUS
 Leptospirosis
 Cortical necrosis
 Renal artery / vein thrombosis
 ATN
 Pathophysiology –intra renal causes

Sepsis –
 Diffuse microvascular injury
 capillary leak
 Reduced GFR

Independent risk factor for mortality

Drugs –
 Tubular toxicity – aminoglycosides , amphotericin B , cisplatin
 Interstitial nephritis – NSAIDS, beta lactams, vancomycin , phenytoin
 Reduced renal perfusion – diuretics , beta blockers , ACE inhibitors ,
NSAIDS
Pathophysiology –intra renal causes

Rhabdomyolysis –
 Tubular injury
 hemoglobin - Increases renal vasoconstriction by inhibiting
production of endothelial NO

Tumor lysis syndrome

 Massive infiltration of renal paranchyma by malignant cells
 Uric acid crystals
 Calcium phosphate crystals
Post renal (5-10%)

 Ureteropelvic junction obstruction

 Ureterovesicular junction obstruction
 PUV
 Ureterocele
 Tumor
 Urolithiasis
 Hemorrhagic cystitis
 Neurogenic bladder
Clinical features

 Pre renal-
tachycardia , poor peripheral perfusion , dry mucous
membranes , hypotension

 Intrinsic renal-
hypertension, peripheral edema, rales , gallop – volume
overload
Neurologic symptoms

 Headache, seizures, lethargy, confusion (encephalopathy)

Etiologic factors
 hypertensive encephalopathy, hyponatremia, hypocalcemia,
 cerebral hemorrhage, cerebral vasculitis, and the uremic
state
Laboratory findings
 Anemia – dilutional , hemolytic ( SLE , HUS , renal vein
thrombosis)

 Leukopenia ( SLE, sepsis)

 Thrombocytopenia ( SLE, HUS, sepsis, renal vein thombosis)

 Hyponatremia ( dilutional)
 Elevated blood urea, s. creatinine, potassium, phosphate
 Hypocalcemia ( hyperphosphatemia)
 osmolality

 C3 levels , ANA (SLE) , ASO , ANCA , anti glomerular

membrane antibodies
 Urine Hypovolemia Acute Acute Glomerulone Obstruction
analysis tubular interstitial phritis
necrosis nephritis

Sediment Bland Broad,browni WBCs,eosino RBCs, RBC Bland or

sh granular phils, cellular casts bloody
casts casts

Protein None or low None or low Minimal but Increased Low

may be >100mg/dl
increased
with NSAIDs

Urine sodium, <20 >30 >30 <20 <20(acute)

mEq/l >40 (few
days)

Urine >400 <350 <350 >400 <350

osmolality
mOsm/kg

Fractional <1 >1 Varies <1 <1(acute)

excretion of >1(few days)
sodium
%
 Urinary indices FeNa – urine Na × plasma creatinine
×100
plasma Na × urine creatinine

prerenal Intrinsic
renal
child neonate Child neonate
U Na (mEq/L) <20 <20 >40 >40
FeNa(%) <1 <2 >1 >3
U osm (mOsm/ >500 >400 <300 <300
kg)
U osm/ P osm >1.5 >2 <0.8-1.2 <1
BU / creat >20.1 >20:1 <20:1 <20:1
Fluid push Urine Urine No response No response
Urine –
 Analysis
 Fractional excretion of sodium
 Osmolality
 Urine for hemoglobin and myoglobin

Radiology –
 Chest X ray ( for fluid over load , cardiomegaly )
 Ultrasonography ( for rena size, identification of obstruction )
 Renal doppler ( for suspeected arterial or venous thrombosis )
 MCU ( for vesico ureteral reflux,or posterior ureteral valve)
Renal biopsy
Indications for renal biopsy in AKI

 RPGN
 Unremitting AKI lasting for >4 weeks especially of unknown
etiology
 Prognostication especially in HUS
 nephrotic/nephritic presentation
 AKI of unknown etiology
 AKI in transplanted kidney
 Early biomarkers - under investigation

 Plasma neutrophil gelatin associated lipocalin ( N-GAL)

 serum cystatin c
 Urinary kidney injury molecule 1 ( KIM-1)
 urinary interleukin 18

 1 -2 days prior to the raise in s. creatinine value

Managemenet
Monitoring
 Vitals
 Weight record twice daily
 Hourly input output recording
 Hourly neurological status observation
 GRBS monitoring
Management

 Stabilization and ABCs

 Optimization of renal perfusion
 Fluid and electrolytes management
 Treatment of hypertension
 Acidosis
 Minimize further renal injury
 Nutrition
 Evaluate if dialysis necessary
 Fluid management

 fluid challenge – 20ml/kg bolus

 Diuretics – inj furosemide 2-3 mg/kg iv bolus

mannitol 0.5g/kg ( for pigment nephropathy )
continuous diuretic infusion
 If no urine after 2-3 hours – fluid restriction should be done

400 ml/m2 + urine output

 Potassium free fluid

 Patient should loss 0.5 – 1% weight

 Drugs tried to increase renal blood flow –

Dopamine ( 2-3 mcg/kg/min)
Fenoldopam ( 0.03 – 0.1mcg/kg/min)
ANP
 HYPERKALEMIA

K > 6meq/dl –
 eliminate potassium from diet
 sodium polystyrene resin (kayaxalate)
1g/kg orally or retention enema
Can be repeated every 2 hrs depending on the sodium overload

K > 7mEq /dl and / or ECG changes –

 Calcium gluconate 10% solution -1.0 mL/kg IV, over 3-5 min
 Sodium bicarbonate -1-2 mEq/kg IV, over 5-10 min
 Regular insulin - 0.1 units/kg, with glucose 50% solution, 1 mL/kg, over 1 hr

Persistent hyperkalemia – dialysis

Hyponatremia
 because of fluid overload
 restrict Na intake to 2- 3 mEq /kg / day
 Symptomatic hyponatremia or s. Na <120mEq /dl should be
treated with – 3% NaCl
 mEq sodium required ---
weight in = 0.6 × kg ×(125− serum sodium in mEq/L).

 Hyperphosphatemia
 Phosphate binders – calcium acetate (20- 65
mg/kg/day)
 Calcium carbonate (20- 65 mg/kg/day)
 sevelamer HCL (400 mg tablets , 2-4 tablets 3
times a day) along with food
Hypocalcemia
 Low phosphate diet
 Phosphate binders
 Iv calcium only in symptomatic cases - tetany
Metabolic acidosis

 Mild metabolic acidosis is common

 Severe metabolic acidosis ( pH < 7.15; serum bicarbonate < 8 mEq/L)
treat with iv bicarbonate till pH increases to 7.2 (bicarb – 12meq /l )
then switch to oral bicarbonate
 Hypertension

Hyper reninemia
MC with – glomerulonephritis , HUS

 Salt and water restriction

 Diuretics
 calcium channel blockers –amlodipine (0.1-0.6 mg/kg/24 hr qd or bid)
 β blockers -propranolol, 0.5-8.0 mg/
 kg/24 hr divided bid or tid;
 Labetalol (4-40 mg/kg/24 hr divided bid or tid)
hypertensive urgency or emergency
 continuous infusions of nicardipine (0.5-5.0 μg/kg/min)
 sodium nitroprusside (0.5-10.0 μg/kg/min)
 labetalol (0.25-3.0 mg/kg/hr)
 esmolol (150-300 μg/kg/min
Anemia
 HB < 7g% PRBC transfusion -`10ml/kg slowly over 4- 6 hrs

Nutrition
 Sodium potassium phosphate restriction
 Protein 2 – 2g/kg in infants
0.8 – 1.2 g/kg in children
 Calories – minimum 60 kcal /kg
 Once dialysis is initiated – protein intake should be increased
 Micronutrient and vitamin supplementation
Management of infections
 Immune system is depressed because of azotemia , concomitant
malnutrition , invasive procedures
 aseptic precautions , oral hygiene
 Long term catheterization of bladder should be avoided

 Signs of sepsis – hypothermia , persistent hypotension

Use of medication –
dose and dosing interval of antibiotics should be modified
 Indications for dialysis in AKI

Anuria/oliguria

 Volume overload with evidence of hypertension and/or pulmonary

edema refractory to diuretic therapy

Persistent hyperkalemia - > 6.5mEq/ l or ECG changes

 Severe metabolic acidosis unresponsive to medical management

 Uremia (encephalopathy, pericarditis, neuropathy)

 Blood urea nitrogen >100-150 mg/dL (or lower if rapidly rising)

Calcium:phosphorus imbalance, with hypocalcemic tetany that

cannot be controlled by other measures
Intermittent hemodialysis
 hemodynamic stability
 highly efficient process
 fluid and electrolyte removal in 3-4 hr
 3-7 times per week based on the patient’s fluid and electrolyte balance
Peritoneal dialysis

 MC neonates and infants

 Hyperosmolar dialysate is infused into the peritoneal cavity
PD catheter
 Fluid is allowed to dwell for 45-60 min
 Cycles are repeated for 8-24 hr/day based on fluid and
electrolyte balance
Outcome

 High morbidity and mortality

 Prognosis is better in patients with oliguric failure, ATN ,

intravascular hemolysis as compared to those with sepsis and
multi organ failure

Predictors of poor prognosis –

 Presence and duration of anuria
 Persistent hypotension / hypovolemia
 Coma
 Mechanical ventilation
Prevention
 Avoiding nephrotoxic drugs
 Good hydration
 Maintain optimal renal perfusion pressure – use of invasive
monitoring in critically sick patients may be useful to achieve
this goal