Acute RenalFailure in NeonatesPrepared byMAGED ZAKARIANICU RESIDENT
AcuteRenal FailureRapid elevation in theconcentration ofBUN, creatinine, andother cellular wasteproducts in the bloodresulting fromdiminished GFR in thekidney.
Causes of ARF in Neonates1. Pre-renal Failure • A decrease of systemic circulation to the kidney. • Renal Hypoperfusion (hypovolemia) Hemorrhage - Dehydration - operative fluid loss - Sepsis - NEC - Hypoalbuminemia • Increased Renal Vascular Resistance Polycythemia - Indomethacin • Renal Hypoperfusion with normovolemia Asphyxia - Septic shock - Heart failure (PDA - Aortic Coarctation).
Causes of ARF in Neonates2. Intrinsic Renal Failure • A damage or necrosis of the parenchyma of the kidney. • Sustained renal hypoperfusion leading to ATN. • Congenital Disorders: Agenesis - Hypoplasia - Dysplasia - PKD (AD – AR). • Bilateral Renal Vein or Artery Thrombosis. • Nephrotoxins: Aminoglycosides - Radiographic contrast media. Maternal use of captopril or indomethacin. • Congenital Infection (Toxoplasmosis or Syphilis).
Causes of ARF in Neonates3. Post-renal Failure • A distal obstruction to urine flow. • Bladder retention: Urethral valves Massive VUR Meningomyelocele (Neurogenic bladder). • Bilateral ureteral obstruction: UPJ or UVJ obstruction - Lithiasis - Fungus ball. • Extrinsic compression: Uroascites (i.e., ruptured urinary tract). Bladder perforation (UAC or direct bladder trauma).
Renal Failure with Hypoxic Ischemic Injury• In the early stages, hypoperfusion results from pump failure and diminished cardiac output due to bradycardia and cardiac depression.• If the problem is not corrected, the injury may progress as vasoconstriction and reduced capillary perfusion result in acute tubular necrosis (ATN) and diminished function.• Renal damage can occur directly from tissue hypoxia and ischemia.
Renal Failure with Hypoxic Ischemic Injury• Measurement of certain urinary indices (urine osmolality, sodium, and the fractional excretion of sodium) may be helpful in differentiating ATN from prerenal disease.• Table 2 shows Urine Indices in Prerenal and Intrinsic RF: Fractional Osmolality Urine Sodium Excretion (mOsm/L) (mEq/L) of Sodium (%) Prerenal Failure > 350 < 20-30 < 2.5 ATN < 350 >30-40 > 2.0
Assessment of a Neonate with ARF• Maternal History (medications, and unusual exposures during the pregnancy, oligohydramnios in the absence of AF leakage or ROM or polyhydramnios)• Prenatal Ultrasonography• Delivery history. Perinatal asphyxia or shock due to volume loss.• Family History including any prior fetal or neonatal deaths. There is a clear genetic basis for PKD and congenital nephrotic syndrome.
Assessment of a Neonate with ARF Anomalies that alert to the possibility of underlying renal defects including Abnormal external auricles or Aniridia (congenital absence of the iris). Microcephaly or Meningomyelocele Pectus excavatum Hemihypertrophy (one side of the body or a part of one side is larger than the other).
Assessment of a Neonate with ARF Anomalies that alert to the possibility of underlying renal defects including A persistent urachus or Exstrophy of the bladder Cloaca or abnormal external genitalia Cryptorchidism or Imperforate anus Limb deformities. Single umbilical artery
Assessment of a Neonate with ARF• Evaluate blood pressure and hydration state.• Hypertension: PKD, ARF, renovascular or aortic thrombosis or obstructive uropathy.• Hypotension: volume depletion, hemorrhage, or sepsis (may lead to ARF).• Edema: ARF, hydrops fetalis, or congenital nephrotic syndrome.
Assessment of a Neonate with ARF• Abdominal mass: two thirds of neonatal abdominal masses are genitourinary in origin (e.g. hydronephrosis, multicystic dysplastic kidney, PKD, RVT, ectopic or fused kidneys, and a renal tumor).• Absence of or laxity in the abdominal muscles: Eagle- Barrett (“prune-belly”) syndrome.• Distention of the bladder: lower urinary tract obstruction or an occult spinal cord lesion.
Prune belly syndrome Eagle-Barrett syndromeMarked wrinkling of the skinand flaccid abdominal wallwhich bulges laterally as aresult of lack of the underlyingabdominal muscles.The triad of findings includeabsence of the abdominalmuscles, urinary tractabnormalities, andcryptorchidism. The abdomenhas a doughy consistency onpalpation, and the abdominalviscera can be felt with unusualease.
Assessment of a Neonate with ARFMicturition • 17% of newborns void in the delivery room • About 90% void by 24 hours and 99% void by 48 hours. • Normal urine output is 1 - 3 mL/kg/hour. • The most common cause of delayed or decreased urine production is inadequate perfusion of the kidneys; however, delay in micturition may be due to intrinsic renal abnormalities or obstruction of the urinary tract.
Assessment of a Neonate with ARFPotter Sequence• Seen in infants with severe bilateral congenital renal disease• Severe oligohydramnios causes fetal deformation by compression of the uterine wall.
Potter Sequence • Characteristic facial features: 1. Epicanthal folds 2. Hypertelorism 3. A crease below lower lip 4. A depressed nasal Associated anomalies bridgeinclude a small compressed 5. A beaked nose chest wall with resulting 6. A receding chin 7. A posteriorly rotated,pulmonary hypoplasia and low-set ears. arthrogryposis.
Assessment of a Neonate with ARFURINALYSIS• A specimen collected by cleaning the perineum and applying a sterile adhesive plastic bag is useful in screening but it may give a false positive urine culture because of fecal contamination.• Bladder catheterization is more reliable but may be technically difficult in preterm infants.• Suprapubic bladder aspiration is the collecting method of choice in infants without intra-abdominal pathology or bleeding disorders.
Assessment of a Neonate with ARFURINALYSIS• The urine should be obtained initially, i.e., before any diuretic or fluid challenge.• USG > 1.025 in pre-renal failure while USG < 1.014 in intrinsic RF.
Assessment of a Neonate with ARFRENAL FUNCTION TESTS• Serum creatinine value measured immediately after birth reflects the maternal rather than infant’s renal function.• Table 1 shows normal creatinine values at birth Gestational Age (wk) Creatinine (mg/dL) 23 to 26 0.77 to 1.05 27 to 29 0.76 to 1.02 30 to 32 0.70 to 0.80 33 to 45 0.77 to 0.90
Assessment of a Neonate with ARF• The standard indicators of renal function are serum levels of BUN and creatinine; their ratio is normally about 10:1.• This ratio may increase when renal perfusion or urine flow is decreased, as in urinary tract obstruction or dehydration.• Because BUN levels are more affected by many factors (eg, nitrogen intake, catabolism, use of corticosteroids) than are creatinine levels, the most reliable single indicator of glomerular function is the serum level of creatinine.
Assessment of a Neonate with ARF• In term babies, the serum creatinine normally rises in the 1st 24-36 hrs after birth, subsequently decreasing and stabilizing at ~ 0.4 mg/dL by 5 days of age.• In preterm infants, the peak value occurs between 2-3 days after birth, and stabilization is delayed until 6 days of age.• It is difficult to use a single value (rather than serial follow up) to diagnose renal failure, except a clearly elevated value beyond the normal range.
Assessment of a Neonate with ARFUltrasonography Indicated in infants with an abdominal mass, renal failure, hypertension, hematuria, oliguria, congenital malformations, or specific findings that suggest anomalies of the urinary tract. A Doppler flow study of the renal arteries and aorta may be helpful in the evaluation of thrombosis in infants with suspected renovascular hypertension or ARF.
Assessment of a Neonate with ARFUltrasonography• Because of relative hypovolemia during the 1st few days of life, repeat US after the 1st week of life if previous findings were normal in a child with previously diagnosed antenatal hydronephrosis before making a final determination that the hydronephrosis has resolved.
Assessment of a Neonate with ARFVoiding Cystourethrography• It involves the instillation of a radiopaque contrast agent into the bladder by urinary catheterization. Films of the urethra during voiding and of the bladder and ureters toward the end of voiding are essential.• Essential in infants with hydronephrosis, renal dysplasia or anomaly or documented UTI.• Used to evaluate the urethra and bladder and ascertain the presence or absence of vesicoureteral reflux.
Assessment of a Neonate with ARFRadioisotopic Renal Scanning• Of value in locating anomalous kidneys, determining kidney size, identifying obstruction or renal scarring. RBF to each kidney and the contribution of each kidney to overall renal function.• It should not be done in the neonatal period because renal immaturity doesn’t allow for accurate estimation of renal function.
Assessment of a Neonate with ARFAbdominal Computed Tomography• Useful in the diagnosis of 1. Renal tumors 2. Renal abscesses 3. Nephrolithiasis.
Clinical Signs of RF 1. Oliguria (urine output < 0.5 ml/kg/h)*. 2. Systemic hypertension. 3. Cardiac arrhythmia. 4. Evidence of fluid overload or dehydration. 5. Decreased activity, seizure and vomiting.*ARF associated with asphyxia is predominantly non-oliguric.Thus, unless Pcr is monitored daily in the severely asphyxiatedneonate, renal failure will be easily missed.
Laboratory Evidence of RF 1. Elevated serum creatinine and BUN 2. Hyperkalemia 3. Metabolic acidosis 4. Hypocalcemia and hyperphosphatemia
Management of ARF Zappitelli and Goldstein, 20081. Treatment of underlying disease2. Avoid/manage fluid depletion/overload3. Correct electrolyte and acid base abnormalities4. Avoid further renal injury5. Drug dosing for renal function6. Provision of adequate nutrition7. Renal replacement therapy.
Fluid Management• Patients with pre-renal failure will often respond to fluid resuscitation, whereas patients with ATN should be treated with volume restriction.• Generally, a safe starting point is to provide insensible losses plus replacement of ongoing losses (urinary, GI, chest tubes) however this may not be appropriate in the setting of acute volume depletion.• Insert a urinary catheter and obtain weights and serum electrolyte levels at least daily.
Fluid Management• Neonates with intravascular volume depletion require vigorous fluid resuscitation. A fluid challenge (20 mL/kg of crystalloid solution, e.g., isotonic saline over 30 min); repeated twice if necessary, after careful monitoring to avoid possible fluid overload.• If anuria persists after 3 fluid boluses (confirmed by bladder catheterization), central venous monitoring may be required to guide further management. • Source: http://emedicine.medscape.com/article/980830-treatment
Fluid Management• Diuretics may convert an oliguric to a nonoliguric ARF, which is more easily managed (no need for fluid restriction, allows for maximal nutritional support).• The current recommendation is that a trial of high dose (2-5 mg/kg) furosemide IV should be attempted with oliguria of < 48 h duration if not responded to adequate hydration.• When renal hypoperfusion or toxic injury is anticipated, administration of fluids and low-dose dopamine have been used to prevent or reverse renal injury.
Fluid Management• Patients who fail to respond to furosemide may respond to Edemex® (bumetanide 5 mg/kg/dose IV), a more potent loop diuretic (not evaluated in acute neonatal oligoanuria).• A diuretic challenge test should be done first in patients thought to be hypervolemic or in heart failure, whereas a fluid challenge should be done first in those thought to be hypovolemic.
Electrolytes Management• Patients with oligo-aneuric RF or ATN should not receive K+ or phosphorus unless they exhibit hypokalemia or hypophosphatemia.• Na+ intake should be restricted to 2–3 mEq/kg/day, together with fluid restriction, to prevent Na+ and fluid retention with resultant hypertension.
Acid Base Management• Metabolic Acidosis Severe acidosis (a plasma bicarbonate concentration of 12 mEq/L or less or plasma pH below 7.20) should be corrected by the administration of IV or oral NaHCO3. Adequate ventilation is necessary in order to exhale the CO2 produced. NaHCO3 may precipitate hypernatremia or hypocalcemia (decreases ionized Ca).
Electrolytes Management1. Serum Potassium Normal level in a non-hemolyzed blood specimen at normal pH is 3.5-5.5 mEq/L Management of Hyperkalemia: 1. Eliminate all sources of K+ from the diet or IVF . 2. Administer a cation exchange resin such as Kayexalate® (sodium polystyrene sulfonate) or Sorbisterit® (calcium polystyrene sulfonate).
Electrolytes ManagementManagement of Hyperkalemia: 3. Administer IV NaHCO3 1 mEq/kg IV over 10 to 30 min (causes a rapid shift of K+ into cells) (used with caution; can precipitate hypocalcemia and Na+ overload). 4. Infusion of glucose and insulin (Glucose 0.5 g/kg; insulin 0.1 U/kg IV over 30 min) 5. Beta-agonists (Salbutamol 0.4 mg (0.08 mL)/kg/dose Q2h via nebulizer; can cause tachycardia).
Electrolytes ManagementManagement of Hyperkalemia: 6. Exchange transfusion with washed packed cells. 7. Calcium gluconate 0.5 to 1.0 mL/kg IV over 5 to 10 min should be administrated in presence of ECG changes (with continuous ECG monitoring for bradycardia and arrhythmias) to counteract the effects of hyperkalemia on the myocardium. 8. The definitive therapy for significant hyperkalemia in oliguric ATN is dialysis
Electrolytes Management2. Serum Sodium Normal level is 134–146 mEq/L Hyponatremia in Renal Failure • Treated by free water restriction. • Serum sodium of < 120 mEq/L requires hypertonic (3%) NaCl infusion (1-3 mL/kg initial dose), especially if CNS dysfunction is present (obtundation or seizure activity).
Adjustment of Medications• Avoid nephrotoxic agents e.g. contrast media, aminoglycosides, and NSAIDs.• The interval of administration of medications with renal elimination (e.g., antibiotics, paralyzing agents, theophylline, antiepileptic drugs, and digoxin) should be adjusted to actual renal function (spontaneous or renal replacement therapy) to avoid toxic levels.• Monitoring drug levels will allow additional adjustments.• When possible, medications with minimal or no renal toxicity should be chosen.
Adjustment of Medications DOSE IN SEPSIS: 20 mg/kg/dose IVI Q12hDose in Renal ImpairmentCr Cl 26-50 mL/min/1.73m2 use normal dose Q12hCr Cl 10-25 mL/min/1.73m2 use half normal dose Q12hCr Cl <10 mL/min/1.73m2 use half normal dose Q24hAn empirically derived formula to estimate CrCl: In Preterm neonates = In Term neonates =
Provision of Adequate Nutrition• If the infant is tolerating oral feedings, maternal human milk or a renal formula that has a low renal solute load and low phosphorus should be used.• Infants who have oliguria frequently cannot receive adequate calories with maternal human milk or formula alone because of the need for fluid restriction. Therefore, high-caloric additives that have low osmolality may be required.
Provision of Adequate Nutrition• If oral feedings are not tolerated, nutrition should be administered IV to provide: 1. A minimum of 50 kcal/kg/day 2. 1-2 g/kg/day of proteins (tailored via measurements of BUN).
Renal Replacement Therapy (Dialysis)• Common Indications For Dialysis: 1. Fluid overload that is unresponsive to diuretics or hinders adequate nutritional support 2. Hyperkalemia with oliguria 3. Symptomatic acid-base imbalances 4. Refractory hypertension 5. Symptomatic uremia (pleuritis, pericarditis, CNS symptoms)
Renal Replacement Therapy (Dialysis)• Before renal replacement therapy is initiated, consideration should be given to the possibility that the patient may have either a dysmorphic syndrome with a very poor prognosis regarding the future quality of life, or severe irreversible multiorgan failure.
Renal Replacement Therapy (Dialysis)• Removes toxins and to maintain fluid, electrolyte, and acid-base balance until renal function returns.• In general, peritoneal dialysis is the preferred method in infants and younger children.
Complications of Renal Failure• Infections (30-70%): Defenses are impaired due to uremia, excessive use of antibiotics and invasive maneuvers.• Cardiovascular complications (hypertension, CHF and pulmonary edema) result from fluid and Na+ retention.• Hyperkalemia (ECG abnormalities and cardiac arrhythmias).
Complications of Renal Failure• Other Complications Include The Following: 1. GI (eg, anorexia, nausea, vomiting, ileus, bleeding) 2. Hematologic (eg, Anemia, Bleeding tendency from abnormal platelet function and, in some patients (e.g., those with RVT), from thrombocytopenia) 3. Neurologic (eg, somnolence, seizures) 4. Electrolyte disturbances (eg, hyponatremia, hyperkalemia, hypocalcemia, hyperphosphatemia) 5. Metabolic acidosis
Mortality from RF in Neonates• Mortality from renal failure in the newborn has been reported to be as high as 25-50%.• The risk is highest in: 1. Intrinsic renal disease. 2. Infants in need for dialysis or mechanical ventilation. 3. Prolonged anuria 4. Absent uptake on renal radionuclide scans.• There is no correlation between peak creatinine values and mortality risk.