Acute kidney injury in Paediatrics 44 slides

Acute kidney injury

1. AKI DR. LAKER GORETTY

2. Terms used Anuria, no urine output. Oliguria - urine output <1 mL/kg per hour in infants, children and adults - urine output <0.5 mL/kg per hour for > 6 hours. Nonoliguria – Urine output for greater than six hours of >1 mL/kg per hour for infants and >0.5 mL/kg per hour for children and adults

3. A K I i n t r o . C o n t . an abrupt loss of kidney function leading to a rapid decline in the : glomerular filtration rate (GFR), accumulation of waste products such as blood urea nitrogen (BUN) creatinine, dysregulation of extracellular volume and electrolyte homeostasis KDIGO defines AKI as : Increase in serum creatinine by ≥ 0.3 mg/dL from baseline within 48 hr ; or Increase in serum creatinine to ≥ 1.5 times baseline within the prior 7 days; or Urine volume ≤ 0.5 mL/kg/ hr for 6 hr

4. I n t r o . C o n t . neonatal AKI - defined as SCr greater than 1.5 mg/dL (133  micromol /L) or an increase of at least 0.2 - 0.3 mg/dL  (17 to 27  micromol /L) per day from a previous lower value SCr at birth is equal to the concentration in the mother (approximately 1 mg/dL [88  micromol /L]). In term infants, SCr declines rapidly in the first two weeks of life ( SCr 0.2 to 0.4 mg/dL [18 to 35  micromol /L])   a n d remain stable through the first year of life . preterm infants, the decline is slower and n o r m a l values are reached over the first one to two months

5. I n t ro . C o n t . The incidence of AKI varies from 2–5% of all hospitalizations to > 25% in critically ill infants and children Functional AKI induced by dehydration is usually reversible with early fluid therapy . However, the prognosis for patients with structural AKI in the intensive care setting with multiorgan failure remains guarded.

6. KDIGO Staging of Acute Kidney Injury stage Serum creatinine Urine out put 1 1.5-1.9 times baseline, OR ≥0.3 mg/dL increase <0.5 mL/kg/hr for 6-12 hr 2 2.0-2.9 times baseline <0.5 mL/kg/hr for ≥ 12 hr 3 3.0 times baseline, OR SCr ≥ 4.0 mg/dL, OR Initiation of renal replacement therapy, OR eGFR < 35 mL/min per 1.73 m2 (< 18 yr) <0.3 mL/kg/ hr for ≥ 24 hr , OR Anuria for ≥ 12 hr

7. Pathogenesis Causes are divided into : Prerenal Renal Post renal causes

8. Prerenal causes Dehydration Gastroenteritis Haemorrhage Burns Sepsis Capillary leak Hypoalbuminemia Cirrhosis Abdominal compartment syndrome Cardiac failure Anaphylaxis

9. Renal causes Glomerulonephritis - - Postinfectious/poststreptococcal . Lupus erythematosus Henoch- Schönlein purpura Membranoproliferative Anti–glomerular basement membrane Hemolytic -uremic syndrome Acute tubular necrosis Cortical necrosis Renal vein thrombosis Rhabdomyolysis Acute interstitial nephritis Tumor infiltration Toxin and drugs Tumor lysis syndrome Vasculitis

10. Post renal causes Posterior urethral valves Ureteropelvic junction obstruction Ureterovesicular junction obstruction Ureterocoele Tumours Urolithiasis Urethral strictures Haemorrhagic cystitis Neurogenic bladder Anticholinergic drugs

11. Prerenal AKI ( prerenal azotemia) characterized by a diminished effective circulating arterial volume, which leads to inadequate renal perfusion and a decreased GFR. Evidence of structural kidney damage is absent. If the underlying cause of the renal hypoperfusion is reversed promptly, renal function returns to normal. If hypoperfusion is sustained, intrinsic renal parenchymal damage can develop.

12. Pre-renal causes in neonates Reduction of effective circulation •Impaired cardiac output ( eg , myocardial injury [perinatal asphyxia], critical congenital heart defects , complete heart block). Sepsis. Third spacing (movement of fluid from the vascular space into the interstitium ) from acute intestinal injury ( eg , necrotizing enterocolitis), IO,peritonitis hypoalbuminemia due to nephrotic syndrome or hepatic failure, capillary leak ( eg , perinatal asphyxia, and hydrops fetalis)

13. Pre-renal RF in neonates c o n t . Neonates are more vulnerable to prerenal AKI than older patients because of the following: Urine concentrating ability is limited , which increases the risk of volume depletion if intake is reduced and/or fluid loss is increased. Insensible water loss through the skin is higher in newborns who have a greater body surface area for their mass compared with older children and adults Interference with normal transition, as may occur with congenital heart disease or perinatal asphyxia, may lead to diminished renal function. reduced ability to compensate for significant hemodynamic changes and may lead to compromised renal function. Impaired autoregulation predisposes to acute kidney injury (AKI) when the BP is reduced

14. At-risk asymptomatic neonates   Very preterm (VPT) infants (gestational age [GA] <32 weeks or birth weight [BW] <1500 g) Perinatal asphyxia Critical congenital heart disease ( T O F , T A P V R , p u l m o nary a t r e s i a , e t c ) Antenatal bilateral hydronephrosis Hydrops fetalis Septic infants treated with parenteral antibiotics Infants who receive antibiotics 

15. Symptom s i n neonates Edema ( common in newborns with AKI ) - can result from fluid overload due to renal dysfunction. Alternatively, other comorbid conditions can contribute to edema, such as capillary leak, heart failure, or hypoalbuminemia. Oliguria or anuria ( no urine output noted by 48 hours of age or a diminished urine output (urine volume less than 1 mL/kg per hour). However, the presence of urine does  not  rule out AKI since some infants are nonoliguric

16. Clinical features Hx vomiting and diarrhea – prerenal causes due to vol depletion, HUS recent pharyngitis present I n g with periorbital edema, hypertension, and gross hematuria - most likely i ntrinsic AKI related to acute postinfectious glomerulonephritis critically ill child with a history of protracted hypotension or with exposure to nephrotoxic medications most likely has ATN A neonate with a history of hydronephrosis seen on prenatal ultrasound studies and a palpable bladder most likely has congenital urinary tract obstruction, probably related to posterior urethral valves

17. Physical examinations Prerenal (suggest an inadequate circulating volume ) Tachycardia, dry mucous membranes, poor peripheral perfusion Intrinsic (from Glomerulonephritis or ATN)- suggestive of volume overload Hypertension, peripheral oedema, rales, cardiac gallop

18. Others rash and arthritis - systemic lupus erythematosus HSP-nephritis Palpable flank masses – renal vein thrombosis, tumors, cystic disease, urinary tract obstruction

19. DIAGNOSIS   made clinically based on the presence of characteristic signs and symptoms, and laboratory findings indicative of an acute change in renal function. Signs and symptoms include edema, decreased or no urine output, gross hematuria and/or hypertension. Laboratory : elevated or rising serum creatinine. An abnormal urinalysis may also provide support for acute injury to the kidney.

20. Neonatal AKI is clinically suspected in a newborn with no urine output by 48 hours of age diminished urine output (less than 1 mL/kg per hour) Edema high blood pressure

21. Ix 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) Urine out put

22. Lab Findings Anemia – dilutional or hemolytic (SLE, renal vein thrombosis, HUS) Leukopenia – SLE, sepsis Thrombocytopenia (SLE, RVT, sepsis, HUS); Hyponatremia – dilutional Metabolic acidosis Elevated serum BUN, creatinine, uric acid, potassium, and phosphate (diminished renal function) Hypocalcemia (hyperphosphatemia)

23. Serum C3 level depressed – PSGN, SLE, or MPGN Antibodies – streptococcal (PSGN), nuclear (SLE), neutrophil cytoplasmic (granulomatosis with polyangiitis, microscopic polyarteritis), or GBM(Goodpasture disease) antigens Hematuria, proteinuria, and RBC or granular urinary casts – intrinsic AKI (glomerular disease and ATN)

24. WBCs and WBC casts with low-grade hematuria and proteinuria – tubulointerstitial disease Urinary eosinophils – drug-induced tubulo-interstitial nephritis

25. Urinary Indices Prerenal AKI Elevated specific gravity (>1.020) Elevated urine osmolality ( UOsm > 500 mOsm /kg) Low urine sodium ( UNa < 20 mEq /L) Fractional excretion of sodium <1% (<2.5% in neonates) Intrinsic AKI Specific gravity of <1.010 Low urine osmolality ( UOsm < 350 mOsm /kg) High urine sodium ( UNa > 40 mEq /L) Fractional excretion of sodium >2% (>10% in neonates)

26. Chest radiography – Cardiomegaly, pulmonary congestion (fluid overload), or pleural effusions. Renal ultrasonography – hydronephrosis and/or hydroureter or nephromegaly Renal biopsy

27. Treatment Medical Management Catheterization (obstruction and urine output) IV NS 20mls/kg over 30 min (if no volume overload/CF). Failure to void after fluid resuscitation in 2hrs, suggests intrinsic or postrenal AKI Hypotension caused by sepsis requires vigorous fluid resuscitation plus infusion of norepinephrine

28. Diuretic therapy Consider only after the adequacy of the circulating blood volume Single IV Furosemide (2-4 mg/kg) , mannitol (0.5 g/kg)(effective in AKI caused by myoglobinuria or hemoglobinuria) Bumetanide (0.1 mg/kg) given as an alternative to furosemide Discontinue if no response to a diuretic challenge Fluid restriction (400mls/m2/24hrs –insensible losses plusamount of fluid equal to urine output for that day) Daily monitoring of fluid intake, urine and stool output, body weight, and serum chemistries

29. Hyperkalemia Serum K+ level > 6 mEq /L Leads to cardiac arrhythmia, cardiac arrest, and death ECG changes – peaked T waves, wide QRS interval, ST segment depression, ventricular arrhythmias and cardiac arrest

30. Initiate procedures to deplete body potassium (if serum K+ >6.0 mEq /L) Eliminate exogenous sources of K+ (dietary, IV fluids, TPN) Sodium polystyrene sulfonate resin (Kayexalate), 1 g/kg/2hr PO or retention enema Severe elevations (>7 mEq /L), esp if accompanied by ECG changes, require emergency measures in addition to Kayexalate 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 Dialysis if all fail

31. Metabolic Acidosis Commonly mild. Due to retention of H+ ions, phosphate, and sulfate, but rarely requires treatment If severe (arterial pH < 7.15; serum HCO3 < 8 mEq /L) or contributes to significant hyperkalemia, treatment is indicated Correct partially by the IV route, generally enough HCO3 to raise the arterial pH to 7.20 (which approximates a serum HCO3 level of 12 mEq /L) Complete correction with oral NaHCO3 after normalization of the serum calcium and phosphorus levels

32. Hypocalcemia Primarily treated by lowering the serum phosphorus level Avoid IV Calcium, except in tetany, to avoid deposition of calcium salts into tissues Low-phosphorus diet Phosphorus binders

33. Hyponatremia Mostly dilutional Correct by fluid restriction rather than NaCl administration Symptomatic hyponatremia (seizures, lethargy) or serum sodium level <120 mEq /L – Hypertonic (3%) saline Acute correction of the serum Na to 125 mEq /L ( mmol /L) should be accomplished using the following formula mEq Na required = 0.6 × weight in kg ×(125− serum Na in mEq/L)

34. Hypertension Results from hyperreninemia associated with the primary disease process and/or expansion of the ECF volume Most common in AKI pts with AGN or HUS Salt and water restriction is critical, and diuretic administration may be useful Isradipine (0.05-0.15 mg/kg/dose, max dose 5 mg qid ) may be administered for relatively rapid reduction in blood pressure.

35. Maintenance (Longer-acting agents) Calcium channel blockers (amlodipine, 0.1-0.6 mg/kg/24 hr qd or divided bid) Beta-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 ) HTN urgency or emergency – continuous infusions Nicardipine (0.5-5.0 ìg /kg/min) Sodium nitroprusside (0.5-10.0 ìg /kg/min) Labetalol (0.25-3.0 mg/kg/ hr ) Esmolol (150-300 ìg /kg/min)

36. Neurologic symptoms Headache, seizures, lethargy, and confusion (encephalopathy) Potential etiologic factors – HTN encephalopathy, hyponatremia, hypocalcemia, cerebral hemorrhage, cerebral vasculitis and the uremic state Benzodiazepines are the most effective agents in acutely controlling seizures and subsequent therapy should be directed toward the precipitating cause

37. Anemia of AKI Generally mild (hemoglobin 9-10 g/ dL ) Results from volume expansion ( hemodilution ) Children with HUS, SLE, active bleeding, or prolonged AKI can require transfusion of packed RBCs if their hemoglobin level falls below 7 g/ dL In hypervolemic patients, BT precipitates HTN, HF and pulmonary edema

38. Slow (4-6 hr ) transfusion with packed red blood cells (10 mL/kg) diminishes the risk of hypervolemia Use of fresh, washed red blood cells minimizes the acute risk of hyperkalemia, and the chronic risk of sensitization during renal replacement therapy. In severe hypervolemia or hyperkalemia, administer BT during dialysis or ultrafiltration

39. Nutrition Restrict sodium, potassium and phosphorus Protein intake should be moderately restricted while maximizing caloric intake to minimize the accumulation of nitrogenous wastes 7/9/2018 TMK 2018 39

40. Dialysis Indications Volume overload with evidence of hypertension and/or pulmonary edema refractory to diuretic therapy Persistent hyperkalemia Severe metabolic acidosis unresponsive to medical management Uremia (encephalopathy, pericarditis, neuropathy) BUN >100-150 mg/ dL (or lower if rapidly rising) Calcium:phosphorus imbalance, with hypocalcemic tetany that cannot be controlled by other measures

41. Inability to provide adequate nutritional intake because of the need for severe fluid restriction (relative) Dialysis support may be necessary for days or for up to 12 wk. Many patients with AKI require dialysis support for 1-3 wk

42. Continuous Renal Replacement Therapy (CRRT) Useful in patients with unstable hemodynamic status, concomitant sepsis, or multiorgan failure in ICU. It is an extracorporeal therapy in which fluid, electrolytes, and small- and medium-size solutes are continuously removed from the blood (24 hr /day) using a specialized pump-driven machine. Usually, a double-lumen catheter is placed into the subclavian, internal jugular, or femoral vein. The patient is then connected to the pump-driven CRRT circuit, which continuously passes the patient’s blood across a highly permeable filter.

43. Prognosis (AKI) Variable and depends on the nature of the underlying disease process Mortality low in AKI due to a renal-limited condition such as PIGN (<1%); and high for multiorgan failure (>90%). Recovery depends on the disorder that precipitated AKI. Good – prerenal causes ATN, acute interstitial nephritis, or tumor lysis syndrome. Poor - Rapidly progressive GN, bilateral RVT, or bilateral cortical necrosis Prolonged mgt of medical – chronic renal insufficiency, hypertension, renal tubular acidosis and urinary concentrating defect.

44. E ND T H A N K Y O U