Ataturk National Children Hospital Children’s Healthcare of Afghanistan Acute Renal Failure Mohebullah Faqiri, MD E-mail: mohabfaqiri@gmail.com September 8, 2016

Acute Renal Failure

Topics to be discussed Definitions. Epidemiology. Causes of ARF . Pathogenesis. Clinical features. Laboratory investigations for Dx & Rx. Complications. Management. Prognosis. Prevention. References.

Definitions: Acute renal failure (ARF) is a clinical syndrome in which a sudden deterioration in renal function results in the inability of the kidneys to maintain fluid and electrolyte homeostasis. Acute impairment of renal functions resulting retention of nitrogenous wastes & other biochemical derangements. Acute-on-chronic renal failure: Occasionally a patient with undetected kidney disease may present with acute onset of anuria or oliguria.

Epidemiology ARF causes 2-8 % admission of pediatrics hospital admissions. ARF causes 8-20% of ICU admissions.

1; pre renal : Acute Gastroenteritis and dehydration. Blood loss. Shock. CHF. Hepato renal syndrome. Cutaneous loss.

2: renal cause. Glomerular. Vascular. Interstitial nephritis. Drug induced. Infections Idiopathic. Glomerular. PIGN. MPGN. RPGN. SLE. HSP. Vascular. HUS. Renal vein thrombosis. Renal vasculitis. Kawasaki disease. Acute tubular necrosis. Ischemic Nephrotoxic.

3. Post renal: Intra-luminal Intra-mural Pelvic malignancies Stone, Blood clots, Papillary necrosis Intra-mural Urethral stricture, BPH, Carcinoma prostate, Bladder tumour, Radiation fibrosis Pelvic malignancies Prolapsed uterus Retroperitoneal fibrosis

ARF Causes

Pathogenesis: Pre-renal failure: ↓ circulatory volume Decrease renal perfusion Activation of autoregatory sys Activates neural and humoral response Sympatic sys activation Renin Ang-Ald syst activation. Release of arginine vasopressin. Stretch receptor stim in Aff art PE2 secretion and local myogenic reflex activation Vasoconstriction. H2o & salt re absorption. Aff art dilatation ↑ secretion of Ang2 Eff arteriole constriction ↑renal BF& GFR.

Intrinsic renal failure Prolonged hypo perfusion. Failure of compensatory mechanisms. Tubular cell injury, necrosis, destruction. Release of epithelial cast. Obstructing of glumerules. Focal break against G.F.R. Tubular contents shifts to interstitial space. Interstitial edema.

Post renal ARF Its includes a variety of disorders characterized by obstruction of the urinary tract. In a patient with 2 functioning kidneys, obstruction must be bilateral to result in ARF. Relief of the obstruction usually results in recovery of renal function except in patients with associated renal dysplasia or prolonged urinary tract obstruction.

Nephrotoxic agents Exogenous Antibiotic (aminoglycoside ,sulfonamide, amphotericin B , tetracycline , imipenum betalactum antibiotic) Chemotherapeutic agents ( cisplatin) Radio contrast media Other drugs ( NSAID , ACE inhibitor , acyclovir) Snake bite Chemical ( insecticide )

Con….. Endogenous Pigments ( Hb , meth Hb , myoglubin ) Crystal ( uric acid , calcium , oxalate) Tumor lysis syndrome

Clinical features Usually anuria or oliguria. Altered sensorium. Convulsions.kkdk Acidotic breathing. Hypertension. Causal: PRE RENAL: vomiting, sunken eye, depressed fontanel, dry mucous membrane, loss of skin turgor, feeble pulse. G.N: hx of recent pharyngitis, hypertension, edema, hematurea, HUS: petechia, pallor, dysentery, bleeding. Acute Intravascular hemolysis: jaundice, pallor, sudden dark red urine, Obs uropathy: interrupted urinary stream, palpable bladder and kidney. U.T calculi: dysuria, hematurea, abdominal colic, Obstruction: complete anuria, ARF-on- CRF: Growth retardation, hypertensive retinopathy, osteodystrophy, severe anemia, hypocalcaemia., small contracted kidney.

Laboratory investigations Blood exam: Anemia, Leucopenia, Thrombocytopenia. Serum electrolytes: Hyponatremia. Hyperkalemia. hypocalcaemia. Hyperphosphatemia Metabolic acidosis.

Lab… Blood urea and creatinine: Urine routine exam: Both are raised due to diminished renal blood flow. Urine routine exam: If glomerulonephritis: hematurea. Proteinuria. RBC casts and granular cast. If Tubulointerstitial . WBC cast, low grade hematuria, proteinuria.

Indices for differentiating pre renal from established RF. Index Pre renal Intrinsic Renal Urinary sodium meq/L <20 >40 Urinary osmolality mOsm/Kg >500 <300 Blood urea to creat ratio >1:20 <1:20 Function excretion of sodium <1 >1 Specific gravity of urine >1,020 <1,010

Investigation con…. Chest radiography: Renal ultrasound. Renal biopsy: cardiomegaly. Pulmonary congestion. Renal ultrasound. Vascularization of pelvicalyceal system. Assessment of renal size. Structure anomaly and calculi. Renal biopsy: Indication of renal biopsy: When etiology is not identified. Un remitting RF lasting more than 2-3 weeks. Suspected drug induced RF.

Complications of ARF Volume overload Heart failure Pulmonary edema Arrhythmia GI Bleeding Hyponatremia Hyperkalemia Hypophosphatemia Hypomagnesaemia Hypocalcaemia Metabolic acidosis Infections Neurologic complications ( seizers, insomnia, drowsiness, coma) Anemia

Management Establish a secure IV line. Draw blood sample for necessary investigations Collect urine sample. Record BP. Catheterize. Carefully intake and output record Daily weight measurement. Urea and creatinine, s.electrolytes, estimated daily base. Frequent E.C.G monitoring.

Daily Fluid therapy. daily fluid requirement: 300-400 cc/m2 /24h. insensible water loss + urine output of last day+ extra renal loss. insensible loss should be replaced with G 5%. Urinary loss and extra renal loss should be replaced with N/2 saline glucose 5%.

Diet: Carbohydrates: 70 %. Lipid : 10-20 %. Protein: 0.5-0.8g/kg/D. Potassium and phosphorous should be restricted. Enough amount of multivitamin and micronutrient should be given.

Cont, Saline or ringer Give 20-30 ml/kg / 45-60 min If no response e.g 2-4 ml/kg/2-3 hr urine, If urine output is increased and but CVP is still low, Infusion of (N.S ) may be continued. Inj. Frusemide.2-3mg/kg If no response e.g 2-4 ml/kg/2-3 hr urine: intrinsic renal failure strongly suspected Dopamine 1-3 µg Mannitol

Renal failure with dehydration: Saline: 20ml/kg/30m. If hydration and shock is improved, give, 90ml/kg/3h. After 3h: if no urine out put but hydration is improved, give furosemide 2ml/kg, after 2-3 h, if No urine output, second dose of furosemide should be given. if hydration is good and BP is low: start Dopamine 2-3µg/kg/min.

Renal failure with fluid overload ( pul.edema) No IV fluid are given. Give furosemide 2mg/kg. Assess after 2-3 hr. if no improve in diuresis, repeat the above dose. If no diuresis, give mannitol: 0.5-1g/kg/3o m. dopamine 5µg/kg/min may be given if there is no hypertension. If all the above measures failed, dialyses is indicated.

Management of complication Hyperkalemia: Metabolic acidosis Infection Hemolysis Tissue damage ECG changes (peak T wave , wide QRS complex ,ST depression , Prolong PR interval

Management of Hyperkalemia If hyperkalemia (> 6meq/dl) Avoidance of fluids , medication , and food containing potassium Sodium poly styrene sulfonate resin (kayexalat) 1gr/kg/day oral or per rectum

Con….. If Hyperkalemia (>7mEq/dl) Calcium gluconate 10% solution 1ml/kg given 3-5 minutes Sodium bicarbonate 1-2 mEq/kg IV over 5-10 minutes Regular insulin 0,5-1 unit /kg with 0.5 gr glucose over 90 minutes Beta 2 agonist drugs ( salbutamol)

Metabolic acidosis Moderate -common no specific treatment Severe acidosis (arterial PH less than 7,15 and serum bicarbonate less than 8mEq/L) or acidosis combined with hyperkalemia requires treatment Sodium bicarbonate 1-2 mEq/kg aiming to raise the serum bicarbonate level to 15-17 mEq .

Hypocalcaemia Hypocalcaemia is primarily treated by lowering the serum phosphorus level. Calcium should not be given intravenously, except in cases of tetany, to avoid deposition of calcium salts into tissues. Patients should be instructed to follow a low phosphorus diet, and phosphate binders should be orally administered to bind any ingested phosphate and increase gastrointestinal phosphate excretion.

Con…… Common agents include sevelamer (Rena gel), calcium carbonate (Tums tablets or Titralac suspension), and calcium acetate (PhosLo).

Con….. Hypernatremia is most commonly a dilutional disturbance that must be corrected by fluid restriction rather than sodium chloride administration. Administration of hypertonic (3%) saline should be limited to those patients with symptomatic hypernatremia (seizures, lethargy) or those with a serum sodium level <120 mEq/L.

Con….. Acute correction of the serum sodium to 125 mEq/L (mmol/L) should be accomplished using the following formula: mEq/L NaCL required=0.6xweight(kg)x(125-serum sodium, mEq/L)

hypertension Symptomatic hypertension (decreased gradually ) Sodium nitroprosid 0.5-1µg /kg/minute by continues infusion Labetalol 0,25-0,3 mg/kg/h Esmolol 150-300µg/kg/minute If there is feature of fluid excess furusamid 1-2 mg /kg

Con…. Asymptomatic hypertension Calcium channel blocker ( nefidepin and amlodipine) Beta blocker ( atenolol) Vasodilator (Hydralazine )

Con…. Neurologic symptoms may include headache, seizures, lethargy, and confusion. Potential etiologic factors include hypornatremia, hypocalcaemia, hypertension, cerebral hemorrhage, cerebral vasculitis, and the uremic state. Diazepam is the most effective agent in controlling seizures, and therapy should be directed toward the precipitating cause.

Con…… Anemia ( Hemolysis , dilutional ) If Hb less than 7gr/dl packed RBC transfusion 5-10 cc /kg

Indication of dialysis Volume over load with evidence of hypertension , pulmonary edema and CHF refractory to diuretic therapy Persistent hyperkalemia ( 6,5mEq/L) Severe metabolic acidosis ( PH less than 7,2 ) Neurological symptoms ( altered sensorium , seizure) blood urea nitrogen greater than 100-150mg/dl Ca/phosphate imbalance with hypocalcaemia tetany

prognosis Optimal management and dialysis can reverse the derangement cause by ARF. Despite advance dialysis mortality rate is 30-40% are reported . Prognosis is good in ATN , intravascular Hemolysis and pre renal failure when complicated factor is absent . Factors associated with high mortality include sepsis , cardiac surgery delayed referral and MOF.

prevention Several condition that cause ARF may be prevented. important measure include. Oral rehydration therapy in diarrhea Avoidance and judicious use of drugs that are nephrotoxic . Care full observation of patients who receiving anti malarial drugs . Good hydration of the patient under going diagnostic procedure with radio contrast media. Force dieresis and use of allopurinol is effective in preventing ARF and patient with TLS.

ARF in newborn Causes: prenatal asphyxia. Shock. septicemia. respiratory distress syndrome. Intravascular volume depletion. following surgery. bilateral renal artery thrombosis( umbilical artery catheterization). Renal vein thrombosis( asphyxiated, dehydrated or polycythemia), hematurea, enlarged flank mass, and azeothemia, Thrombocytopenia. renal failure may occasionally, be the first manifestation of congenital anomaly of the urinary tract.

Ranal failure is suspected in pressence of the following. Oliguria( 1ml/kg/hr). Blood creatinine is 1.2 mg/dl ).

Management Principle of management is similar to that of the older children: Fluid given should be limited to: Insensible( 30ml/kg/D for full term). 5o-100 ml/kg/D for preterm ) Extremely premature neonates nursed in radiant warmer, requires extra fluid. Systolic BP>95-100 mmHg: may need treatment.

Dialysis Some excepting in neonatal dialysis: Peritoneal dialysis is preffered for neonates. PD may cause respiratory embarrassment or apnea. Hypothermia should be avoided by the careful warming of the dialysis fluid.

Prognosis: Mortality rate: Outcome is related to underlying condition. Mortality rate for oliguric renal failure are about 40-50 %. Nonoliguric patient has better prognosis. Outcome is related to underlying condition.

Indications for transplantations When no systemic disease is present. When GFR is less than 3oml /1.73m2 .

Reference OP Ghai Nelson text book of Pediatrics Basis of Pediatrics Care of Newborn Pediatrics Nephrology Rudolph Pediatrics Emergency

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