Acute renal failure DR AQEEL ALGHAMDI MBBS,DCH,JBCP,ABP,FBN consultant pediatric nephrology

Acute renal failure

Acute kidney injury (AKI) is defined as the abrupt loss of kidney function that results in 1 ) a decline in glomerular filtration rate (GFR), 2 ) retention of urea and other nitrogenous waste products, 3 ) dysregulation of extracellular volume and electrolytes

AKI is manifested by increases in nitrogenous waste products (BUN) and serum creatinine, and, in some cases, a concomitant reduction in urine output (less than 0.5 to 1 mL/kg per hour

CLASSIFICATION pRIFLE — pRIFLE is a pediatric modification of the adult RIFLE classification and consists of three graded levels of injury (Risk, Injury, and Failure) based upon the magnitude of change in estimated GFR (eg, changes in serum creatinine) or urine output, and two outcome measures (Loss of kidney function and End-stage renal disease)

CLASSIFICATION Pediatric RIFLE Classification of acute kidney injury pRIFLE stage Estimated creatinine clearance (eCCl) Urine output R = Risk for renal dysfunction eCCl decreased by 25% <0.5 mL/kg per hour for 8 h I = Injury to the kidney eCCl decreased by 50 % <0.5 mL/kg per hour for 16 h F = Failure of kidney function eCCl decreased by 75 % or eCCl <35 mL/min per 1.73 m2 <0.3 mL/kg per hour for 24 h or anuria for 12 h L = Loss of kidney function Persistent failure >4 weeks E = End-stage renal disease Persistent failure >3 months

GFR Glomerular filtration rate estimate by Schwartz formula Glomerular filtration rate = k * Height / Serumcreatinine

uop Anuria, no urine output Oliguria defined as urine output <1 mL/kg per hour in infants, and in children and adults, urine output <0.5 mL/kg per hour for greater than six hours Nonoliguria – The majority of neonates with AKI will have nonoliguric AKI, even those with moderate to severe impairment of kidney function Polyuria – Some patients with a urinary concentrating defect will present with polyuric AKI, particularly those with acute tubular necrosis

Causes and mechanisms Vascular – Blood from the renal arteries is delivered to the glomeruli. Interruption of perfusion to the kidneys results in prerenal AKI. ●Glomeruli – Ultrafiltration occurs at the glomeruli forming an ultrafiltrate, which subsequently flows into the renal tubules. Glomerular injury resulting in disruption of glomerular filtration rate (GFR) is one of the major causes of intrinsic AKI.

●Renal tubule – Reabsorption and secretion of solute and/or water from the ultrafiltrate occurs within the tubules. Acute tubular necrosis due to nephrotoxins or hypoperfusion is one of the major causes of intrinsic AKI.

●Urinary tract – The final tubular fluid, the urine, leaves the kidney, draining sequentially into the renal pelvis, ureter, and bladder, from which it is excreted through the urethra. Postrenal AKI is due to obstruction of urine anywhere along the urinary tract in a single kidney, and in patients with two kidneys, bilateral obstruction usually at the bladder or urethral level

Prerenal disease is caused by reduced renal perfusion. It is the most common form of AKI and is due to hypovolemia (bleeding or gastrointestinal, urinary or cutaneous losses), or reduction of effective circulation (eg, heart failure, septic shock, and cirrhosis). (GFR) is reduced, renal tubular function remains intact with avid reabsorption of sodium and water in response to renal hypoperfusion, leading to oliguria. When normal renal perfusion is restored, urine flow and GFR usually return to normal.

● Intrinsic renal disease – Intrinsic or intrarenal AKI is characterized by structural damage to the renal parenchyma. The most common causes of intrinsic disease are prolonged hypoperfusion, sepsis, nephrotoxins, or severe glomerular diseases. ● Postrenal disease – Postrenal or obstructive AKI is typically the result of congenital or acquired anatomic obstructions to the lower urinary tract

Intrinsic AKI — The most common underlying etiology is prolonged renal hypoperfusion Vascular disease — include thrombosis (arterial and venous), hemolytic uremic syndrome, and vasculitides Glomerular disease — The principal cause of AKI is acute glomerulonephritis

Tubular and interstitial disease — Prolonged prerenal AKI with reduction in renal perfusion, and tubular nephrotoxins are important causes of intrinsic AKI Common exogenous nephrotoxins include aminoglycosides, amphotericin B, contrast agents, calcineurin inhibitors, and cisplatin

Intrinsic AKI can also be induced by the release of endogenous nephrotoxins such as myoglobinuria due to rhabdomyolysis and hemoglobinuria due to intravascular hemolysis

Postrenal AKI — Postrenal AKI is due to bilateral urinary tract obstruction or obstruction of the urinary tract of a solitary kidney. Causes of postrenal AKI include renal calculi, clots, neurogenic bladder, and medications that cause urinary retention

Clinical presentation In most children, AKI presents with signs and symptoms that result directly from alterations of renal function. * edema (due to progressive fluid accumulation), *decreased or no urine output, *gross and microscopic hematuria, and/or hypertension

HISTORY ●A short duration of vomiting, diarrhea, or decreased oral intake associated with decreased urine output suggests prerenal AKI. ●A history of bloody diarrhea 3 to 7 days prior to the onset of oliguria suggests hemolytic uremic S. ●A history of pharyngitis or impetigo a few weeks prior to the onset of gross hematuria or edema suggests PSGN

●In hospitalized patients, nephrotoxic medications or periods of hypotension are associated with intrinsic AKI. ●Other systemic complaints (eg, fever, joint complaints, and rash) may be seen in patients with autoimmune diseases or vasculitides, such as Henoch-Schönlein purpura (IgA vasculitis).

Physical examination The physical examination should include measurement of blood pressure assessment for edema and recent weight gain, signs of systemic disease, such as rash or joint disease

Laboratory and imaging evaluation Laboratory tests and renal imaging that may be useful in determining the underlying etiology of AKI include: ●Urinalysis ●Fractional sodium excretion to differentiate between pre- and intrinsic AKI ●Renal ultrasound

URINALYSIS ●Muddy brown granular casts and epithelial cell casts are highly suggestive of intrinsic AKI or acute tubular necrosis (ATN ● red cell casts is diagnostic of GN. The concurrent finding of dysmorphic red cells and heavy proteinuria indicates an active “nephritic” urinary sediment, which is also commonly associated with glomerulonephritis

●Pyuria with white cell, granular, or waxy casts are suggestive of tubular or interstitial disease, or urinary tract infection. White cells and white cell casts may also be seen in acute glomerulonephritis. ●A positive response for heme on a urine dipstick in the absence of red blood cells in the sediment is seen in patients with hemolysis or rhabdomyolysis. ●The urinalysis in children with prerenal AKI is typically normal

●Urine specific gravity – Loss of concentrating ability is an early and almost universal finding in ATN with a urine specific gravity below In contrast, urine specific gravity greater than is suggestive of prerenal disease. Urine osmolality is a more accurate measure of concentrating ability. Patients with ATN generally have urine osmolality below 350 mosmol/kg, whereas patients with prerenal disease usually have values above 500 mosmol/kg

Fractional excretion of sodium — The fractional excretion of sodium (FENa) is the most commonly used laboratory test to differentiate between prerenal AKI and intrinsic disease due to ATN. FENa is calculated from measured concentrations of urinary sodium (UNa) and creatinine (UCr), and plasma sodium (PNa) and creatinine (PCr): UNa x SCr FENa, percent = ——————— x 100 SNa x UCr

●A FENa below 1 percent suggests prerenal AKI, in which the reabsorption of almost all the filtered sodium represents an appropriate response to decreased perfusion ●A FENa above 2 percent suggests ATN ●A FENa between 1 and 2 percent is nondiagnostic

Serum creatinine — The most common laboratory test used to identify reduced glomerular filtration rate (GFR) as an indication of AKI is serum creatinine ●Newborn – 0.3 to 1 mg/dL (27 to 88 micromol/L) ●Infant – 0.2 to 0.4 mg/dL (18 to 35 micromol/L) ●Child – 0.3 to 0.7 mg/dL (27 to 62 micromol/L) ●Adolescent – 0.5 to 1 mg/dL (44 to 88 micromol/L

●Complete blood count – Microangiopathic hemolytic anemia associated with thrombocytopenia in HUS Eosinophilia and/or urine eosinophiluria may be present in some cases of interstitial nephritis ●Complement studies including C3, C4, CH50, and AH50 – Hypocomplementemia is seen in patients with poststreptococcal glomerulonephritis (PSGN), shunt nephritis, and nephritis associated with subacute bacterial endocarditis

●Serologic testing for streptococcal infection – ●Elevated serum levels of aminoglycosides are associated with ATN ●Uric acid – AKI may result from markedly elevated uric acid levels, which may occur in children with tumor lysis syndrome secondary to chemotherapy treatment of childhood leukemia or lymphoma

Renal imaging — A renal ultrasound should be considered in all children with AKI of unclear etiology Renal biopsy — A renal biopsy is rarely indicated in AKI

The most common differential diagnosis for acute kidney injury (AKI) is the initial presentation of chronic kidney disease (CKD).

MANAGEMENT ●Fluid management ●Electrolyte management ●Nutritional support ●Adjustment of drug dosing ●Renal replacement therapy ●Specific pharmacologic therapies

PROGNOSIS AND OUTCOME AKI is associated with increased mortality and long- term morbidity. Mortality — In the United States, reported in- hospital mortality rate of children with AKI is about 15 percent The mortality rate is lower among children who develop non-intensive care unit (ICU) setting, with reports ranging from 1.5 to 9.5 percent. in the ICU setting about 30 percent