ACUTE RENAL FAILURE

Academic Half Day

February 9, 2012

Objectives

To review: the etiologies of acute kidney injury (AKI) in the pediatric population the work-up/diagnosis of AKI the management of AKI What is AKIs?

“abrupt reduction in kidney function as measured by a rapid decline in GFR”

Previously known as Acute Renal Failure

Now failure represents one end of the spectrum

Etiology is variable

Definitions/classifications have varied in the literature…

Classification - pRIFLE

Risk

Injury

Failure

Loss

End-stage

U/O <0.5cc/kg/h x 8h

Failure > 3 months

Persistent failure >4wks

eCCl dec 50%U/O

<0.5cc/kg/h x 16h

<0.3cc/kg/h x 24h/Anuric x 12h

eCCl dec 75%/ < 35ml/min/1.73m2

eCCl dec 25%

Leads to: Impaired excretion of nitrogenous waste Impaired water and electrolyte balancing Impaired acid/base regulation Impaired vascular tone regulation

Burden of disease

Incidence (US): 0.8/100 000; ~1/10 in ICU Increasing

Independent risk factor for ICU mortality

Increases length of hospital stay

May lead to chronic renal failure (40-50% ICU)

Etiologies: a general approach

Though likely multifactorial, can be divided into:

Pre-renal Renal Post-renal

Pre-renal causes:Any cause which results from kidney seeing to little blood flow

Volume deplete: GI

Vomiting Diarrhea

Bleeding Trauma Surgery

Diuresis Diabetes - DM, DI Drugs

Kidney sees less volume: Sepsis CHF Cirrhosis Vascular - also consider in renal

RAS Thrombus Takayasu, PAN, KD

Drugs NSAIDs ACEi ARBs

Renal causes

Vascular:Microvasculature: Sickle cell disease HUS Tumour lysis rhabdomyolysis

?Syndromes Hepatorenal Cardiorenal Pulmonary-renal

Glomerular:Glomerulonephritis:•Post-infectious•membranoproliferative•SLE•HSP

Tubulo/Interstitial:Acute tubular necrosis -secondary to nephrotoxic insults or poor perfusion

Acute interstitial nephritis -drugs -infxn

Cortical dysplasia

-hypoxia/ischemia->infarct -toxins/severe HUS

?Sepsis inflamm, not all volume related

Hemolytic UremicSyndrome

History of Ecoli, Shigella, shiga-toxin…

Atypical (non-diarrhea, non-shiga-toxin)

Hemolytic anemia with fragmented RBCs

Thrombocytopenia

Renal injury

CNS, liver, pancreas can also be affected

Post-infectious glomerulonephritis

Occurs in ages 5-12, post-GAS.

Presentation can be asymptomatic to nephritis complete with gross hematuria, proteinuria, HTN, edema

Labs: abnormal urinalysis, low complement

Rx: supportive.

Prognosis: most make complete recovery.

HSP

-Causes renal issues d/t IgA deposition.

-A/W palpable purpura, arthritis, abdo pain.

-Renal more likely to be an issue in older kids

-Rx: if crescenteric, GN - steroids.

-prognosis: often relapses. Can have late deterioration even if full recovery. 10-30% adults go on to have end-stage disease.

Acute TubularNecrosis

Describes an end effect of tubular damage… Secondary to perfusion insults Secondary to toxins

Change in blood flow, obstruction and passive filtrate backflow into tubular cells can cause a cycle leading to further death…

AIN

Drugs (71%) - 1/3 antibiotics Penicillins, cephalosporins, NSAIDs, sulfonamides, cipro,

rifampin, PPIs, allopurinol… and more

Infection (15%) Strep, Legionella, leptospirosis, CMV, EBV… many

Tubulointersitial nephritis and uveitis (5%)

Autoimmune: SLE, Sjogren’s

Sarcoidosis

Idiopathic (8%)

Nephrotoxins

Vascular effect ACEi, cyclosporine, tacrolimus

Tubular effect Proximal: aminoglycosides, amphotericin B,

cisplatin, immunoglobulins, contrast Distal: NSAIDs, ACEi, lithium, cyclophosphamide Obstruction: sulfa, acylovir, methotrexate

AIN

Post-renal causes

Two kidneys - distal or bilateral proximal obstruction

Single kidney - obstruction anywhere Posterior urethral valves Ureteropelvic junction obstruction Ureterovesicular junction obstruction Ureterocele Stones Tumour Hemorrhagic cystitis Neurogenic bladder

On history…

? pre-renal: Vomiting, diarrhea, bleeding, sepsis, dec PO Drug use - inc NSAIDs

? renal: Bloody diarrhea? (HUS) Recent illness? (PSGN) Crush

injury? Drug use: aminoglycosides, antifungals, chemo Associated lung/heart/liver symptoms? (dual organ)

? post-renal:

On physical…

Pre-renal: Dehydration Signs of heart failure/cirrhosis/sepsis

Renal: Edema (nephrotic syndrome) Purpura (HSP

Post-renal: palpable bladder?

What to order?

BUN, Cr, lytes, fractional excretion of sodium

Urinalysis

On labs…

NORMAL:

-pre-renal (may be concentrated)

-post-renal

-ATN

ABNORMAL:-brown granular/epithelial casts = ATN-red cell casts = glomerulonephritis-proteinuria = glomerular-pyuria, white cell casts = UTI or glomerulonephritis (post-infxn)-hematuria = AIN, vasculitis, infarction, obstruction

Everyone gets a urinalysis…

And even more information from urine…

Urine osmolality: Typically low in ATN (<350 mosmol/kg) Typically high in pre-renal disease (>500)

Urine volume: Often low, especially given criteria for AKI. However, some ATN is non-oliguric

Urine eosinophils

Urine sodium…

Sodium excretion

Why? Helps distinguish pre-renal vs ATN… >30-40 mEq/L = ATN <10 mEq/L = effective volume depletion

(20-30 in infants) BUT what if there is a large urine output?

Fractional Excretion of Sodium

FENa compensates for the urine output…

UNa x PCr

PNa x UCr

…can also be thought of as

UNa/PNa

UCr/PCr

<1% --> pre-renal disease

1-2% --> ??

>2% --> ATN

Bloodwork…

CBC: look for MAHA, thrombocytopenia

Extended lytes. Renal injury can result in: Hyperkalemia Hyperphosphatemia Hypocalcemia Metabolic acidosis

Other options, depending on history: ANCA,

ANA, ASOT, complement, drug levels…

And of course, creatinineCreatinine is usually elevated

Normal Cr varies by age

Note Cr can NOT be used to estimate GFR in acute kidney injury…

This is why the search is on for a “troponin of the kidneys”

Age Normal range (umol/L)

Newborn 27-88

Infant 18-35

Child 27-62

Adolescent 44-88

Troponin of the kidneys?

Unfortunately, not yet… Some ideas: Urinary neutrophil gelatinase-associated lipocalin

(NGAL) Increased 50-fold, and 24h before serum Cr Has been shown to predict AKI severity in SLE, HUS, renal

transplant patients

Kidney injury molecule - 1 (KIM-1) IL-18

Imaging

Ultrasound - in all children if etiology unclear # of kidneys Size of kidneys Obvious parenchymal damage Obstruction Thrombus/vessel occlusion

Renal biopsy

Only when diagnosis remains unknown, or

there is a failure to respond to treatment

Approach summary:

Ultrasound

Low ECF volume-GI loss-diuresis

-hemorrhage

Low vol to kidney-heart failure

-meds (NSAIDs, ACEi, ARB)-vascular disease

PRE-RENAL

-bilateral ureteric obstruction-single kidney + ureter obs

-bladder/urethra obs

POST-RENAL

NORMALurinalysis

Artery-RAS

-Takayasu, PAN, KD-can think of drugs here too

Veins-thrombosis

Vascular disorders

Glomerular disorders

AIN-drugs

-infection-autoimmune

ATN-ischemia-contrast

plugged-crystals-globins-drugs

Tubular disorders

Parenchymal disorders

RENAL

ABNORMALurinalysis

pRIFLE met-estimated CrCl

-oliguria

Treatment

Principles:

1. FEN

2. Avoid complications

3. Treat underlying cause

Generally pediatric nephrology will be involved.

FEN - fluids

Child can be hypo-, eu- or hypervolemic.

FLUID STATUS

Crystalloids (NS)-bolus, rpt

-no change?Consider invasive monitors

HypovolemiaGoal:

maintain renal perfusion

Monitor ins/outs-daily weights

-ins=outs + insensibles

Euvolemia

Fluid removal/restriction-furosemide (2-5mg/kg)

-no change?Consider RRT

HypervolemiaType Title Here

HTN can occur and is usually secondary to volume overload.Treatment based on diuretic response, severity.

FEN - electrolytes

Hyperkalemia - if severe (>7) - C BIG K Die… Don’t give K (IVs, low K diet) stabilize the cardiac membrane - IV calcium

gluconate Move K ECF -> ICF by:

Insulin (with glucose) Sodium bicarb Beta agonists

Remove K from the body - kayexalate Can try diuretics - unlikely to do enough RRT if the above doesn’t work

FEN - electrolytes

Acidosis Respiratory compensation can be enough Sodium bicarb ONLY if life-threatening and/or

contributing to hyperkalemia Def not if pH >7.2 or bicarb >14mEq/L Can decrease Ca further -> seizures Can increase intravascular volume

If refractory volume overload, hypernatremia -> RRT

FEN - electrolytes

Hyperphosphatemia: Low phosphate diet Binders

Hypocalcemia: Calcium gluconate Can pre-empt if sodium bicarb being given

FEN - Nutrition

AKI is a catabolic state

Ensure adequate calories

- 120kcal/kg/d in infants

- usual maintenance for children

PO -> enteral -> TPN

If fluid balance off with adequate nutrition: RRT

Avoid complications

Including making things worse…so no:

Aminoglycosides

NSAIDs

Antifungals

Immunosuppressive drugs

Contrast media

Renal Replacement Therapy (RRT)

Indications:

1. Uremia s/s - pericarditis, neuropathy, decline

2. Azotemia - BUN >36

3. Refractory fluid overload - HTN, pulm edema, CHF

4. Refractory hyperK, hypo/hyperNa, acidosis

5. Nutritional support with fluid balance issues

RRT

Options:

Continuous renal replacement therapy

Peritoneal dialysis

Hemodialysis

Prognosis

Mortality: 60% (critically ill)

20-25% go on to have some degree of chronic renal issues

Take home points

Etiology: Best divided into pre-, renal and post-renal

Work-up: Urinalysis, ultrasound, bloodwork…

Treatment:Fluids - close balanceElectrolytes - esp K, PO4, CaAcidosisNutritionDialysis - talk later today

ReferencesAkcan-Arikan A, Zappitelli M, Loftis L, Washburn K, Jerrerson L, and Goldstein S. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney International; 2007: 71: 1028-35.

Basu R, Devarajan P, Wong H, and Wheeler S. An update and review of acute kidney injury in pediatrics. Pediatric Critical Care Medicine; 2011: 12(3): 339-47.

Imam A. Clinical presentation, evaluation, and diagnosis of acute kidney injury (acute renal failure) in children. Uptodate. Accessed Feb 8, 2012 at http://www.uptodate.com.ezproxy.lib.ucalgary.ca/contents/clinical-presentation-evaluation-and-diagnosis-of-acute-kidney-injury-acute-renal-failure-in-children?source=search_result&search=acute+kidney+injury&selectedTitle=2~150

Imam A. Prevention and management of acute kidney injury (acute renal failure) in children. Uptodate. Accessed Feb 8, 2012 at http://www.uptodate.com.ezproxy.lib.ucalgary.ca/contents/prevention-and-management-of-acute-kidney-injury-acute-renal-failure-in-children?source=search_result&search=acute+kidney+injury&selectedTitle=1~150

Kliegman R, Stanton B, Geme J, Schor N, and Behrman R. Nelson Textbook of Pediatrics 19th e.

Elsevier; 2011: 1814-22.