ACUTE KIDNEY INJURY IN CHILDREN.

AKI in hospitalized children is associated with increased mortality

ICU setting mortality rates associated with AKI are higher: up to 30 to 44%

Highest mortality rates are seen in infants, patients with multiorgan failure and those on renal replacement therapy (KRT)

Children with AKI are at long-term risk for developing CKD

Patients with moderate to severe AKI should be followed annually to detect signs of CKD (eg, hypertension and proteinuria).

1. ACUTE KIDNEY INJURY IN CHILDREN (AKI) Presenter Dr. Beatrice Kyomugisa Paediatrician Fort Portal Regional Referral Hospital

2. Outline Definition Staging Epidemiology Classification of AKI Causes of AKI Risk factors Clinical features Complications Investigations DDx Management Prevention Prognosis

3. Definition Abrupt loss of kidney function that results in a decline in glomerular filtration rate (GFR), retention of urea and other nitrogenous waste products, and dysregulation of extracellular volume and electrolytes. AKI is defined as any of the following: Increase in Serum Creatinine ( SCr ) by ≥0.3 mg/dl (≥ 26.5 umol /l) within 48 hours OR Increase in SCr of ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days OR Urine volume <0.5 ml/kg/h for 6 hours.

4. Staging KDIGO , 2012 proposed a combined definition for AKI in children & adults combining aspects of AKIN, pRIFFLE and RIFFLE

5. Staging of acute kidney injury in children: Kidney Disease Improving Global Outcomes (KDIGO) criteria Stage Serum creatinine Urine output 1 Increase to 1.5 to 1.9 times, or increase of ≥0.3 mg/dL (≥26.5 mcmol /L) <0.5 mL/kg/hour for 6 to 12 hours 2 Increase to 2 to 2.9 times baseline <0.5 mL/kg/hour for ≥12 hours 3 Increase >3 times baseline,  or SCr ≥4 mg/dL (≥353.6 mcmol /L),  or Initiation of kidney replacement therapy,  or eGFR <35 mL/min per 1.73 m 2  (<18 years) <0.3 mL/kg/hour for ≥24 hours,  or Anuria for ≥12 hours

6. AKI or NOT Change of 0.7mg/dL within 24 hours Fold change of 2 using the repeat creatinine (Stage 2) What is the baseline value? Use the value from follow-up Estimate baseline 2 year old Creatinine on admission: 0.6mg/dL or 53 umol /L Repeat creatinine: 1.3mg/dL or 106.1 umol /L

7. Limitations of creatinine AKI definitions Serum creatinine ( SCr ) is highly affected by muscle mass, age and altered by malnutrition SCr is affected by volume status, where volume overload can dilute SCr concentrations, leading to a potential masking of SCr increase Definitions are based on baseline SCr which is usually unknown SCr and/or urine output changes late in the pathophysiology of AKI; up to 72 h after injury has occurred

8. Epidemiology Globally, 85% of acute kidney injury (AKI) cases occur in low-and-middle-income countries. KDIGO criteria: 11-59% Uganda: 35-46%

9. Etiological classification of AKI

10. Etiopathogenesis of AKI Pre renal Intrinsic (Renal ) Post renal Dehydration Hemorrhage Burns Sepsis Cardiac failure Dehydration Diuretics Burns Shock Nephrotic syndrome Sepsis Anaphylaxis Antihypertensives Prolonged ischemia Nephrotoxins Persistent hypotension Sepsis Hemolytic uremic syndrome Thrombosis Interstitial nephritis Infections Malignancy Post-infectious GN Rapidly progressive GN Henoch- Schönlein purpura Acute tubular necrosis (Malaria) Posterior urethral valves Ureteropelvic junction obstruction Urolithiasis Malignancy Blood clots Neurogenic bladder Medications that cause urinary retention

11. Clinical features Edema Hypertension Acute weight gain Decreased or no urine output Gross and microscopic hematuria Poor urinary stream History A short duration of vomiting, diarrhea, or decreased oral intake associated with decreased urine output suggests prerenal AKI History of bloody diarrhea 3 to 7 days prior to the onset of oliguria suggests hemolytic uremic syndrome

12. Cont ….. History of pharyngitis or impetigo a few weeks prior to the onset of gross hematuria or edema suggests poststreptococcal glomerulonephritis. History of drug use: nephrotoxic medications(NSAIDs, aminoglycosides) or prolonged periods of hypotension are associated with intrinsic AKI. A diligent search for all drugs and medications ingested is especially important, even when another obvious cause for AKI is evident. Systemic complaints of fever, joint pains, and rash i.e Henoch- Schönlein purpura, systemic lupus erythematous Burns , bleeding and surgery

13. Physical examination Measure blood pressure e.g hypo or hypertension Assess for edema Weigh the patient to determine weight gain Rash: Henoch- Schönlein purpura, systemic lupus erythematous Joint tenderness or swelling: Henoch- Schönlein purpura, SLE) Poor urinary stream Palpably enlarged bladder Palpably enlarged kidneys: Polycystic/ multicystic kidney disease, Renal vein thrombosis Assess for shock

14. Complications Chronic kidney disease Electrolyte abnormalities e.g hyperkalemia, hyperphosphatemia Metabolic acidosis Uremic encephalopathy (seizures) Uremic gastritis and bleeding Uremic pericarditis and pleuritis Complications of dialysis

15. Investigations Urinalysis: urinalysis in children with prerenal AKI is typically normal. Glomerulonephritis (RBC or WBC casts); ATN (granular casts); acute interstitial nephritis (eosinophilia) Complete blood count: Leucopenia (SLE , sepsis), thrombocytopenia (sepsis, HUS) , anaemia (dilutional or hemolytic e.g. HUS, SLE) RFTs ( blood urea nitrogen (BUN) and creatinine ) and electrolytes (K, Na, phosphate, Ca, Mg) Blood gas: metabolic acidosis, compensated or not Complement studies e.g C3, C4, hypocomplementemia is seen in patients with poststreptococcal glomerulonephritis (PSGN)

16. Autoimmune work-up: ANCA, ANA, C3 and C4 for glomerulonephritis Renal ultrasound: Increased echogenicity, kidney size/ number/ structure , hydronephrosis/ hydroureter Renal vessel Doppler study: increased resistive indices with ATN and thrombosis Computed tomography/magnetic resonance: trauma, stones Radionucleotide scan: determine level of obstruction and assess function Voiding cystourethrogram ( vCUG ): diagnose obstruction ( esp posterior urethral valves) Cont ……

17. Differential diagnosis Chronic kidney disease Heart failure Acute malnutrition (edematous) Nephrotic syndrome Liver cirrhosis Acute tubular necrosis Acute glomerulonephritis Hemolytic uremic syndrome

18. General principles of management of (AKI) F luid management: Assess fluid status, if edematous give diuretics(IV Furosemide 2-5mg/kg/dose) if hypovolemic give fluids (N/saline), if euvolemic give maintenance fluids. R enal replacement therapy: Dialysis (when all measures fail) A djustment of drug dosing: withhold or adjust nephrotoxic drugs N utritional support: Restrict all K+ containing foods (fruits/juices, packed foods) and salt intake E lectrolyte management: Manage hyperkalemia, hyperphosphatemia S pecific pharmacologic therapies: Treat HTN and specific RX of the underlying cause (Malaria: antimalarials) S upportive measures: Fluid input and output/ prescription, daily dipstick, RFTs and electrolytes, measure TPR,SPO2, BP and weight .

19. Management of hyperkalemia by severity Severity Management Mild hyperkalemia ( 5.5 to 6.0 mEq/L) Oral Kayexalate , + nebulized salbutamol Moderate hyperkalemia ( 6.1 to 6.9 mEq/L) Oral Kayexalate , nebulized salbutamol IV calcium gluconate Insulin/ glucose Diuretics eg Furosemide Severe hyperkalemia ( ≥7 mEq/L ) Oral Kayexalate , nebulized salbutamol IV calcium gluconate Insulin/ glucose Diuretics eg Furosemide Dialysis

20. Management of hypocalcaemia and hperphosphatemia Hypocalcemia Managed with calcium supplements Vitamin D 1 alpha or 1,25 hydroxycholecalciferol (this is especially important in CKD) Hyperphosphatemia Phosphate binders; Calcium carbonate available on market

21. Prevention of acute kidney injury Multidisciplinary approach Identify the patients at risk of AKI eg DKA, shock, sepsis, malaria Avoidance and substitution of nephrotoxic drugs eg gentamycin , NSAIDs Avoidance of hypovolemia by fluid administration eg Diarrhoea and vomiting Avoid hypotension Perform RFTs and electrolytes early.

22. Differences between AKI and CKD in children Finding Acute kidney injury Chronic kidney injury Serum BUN and Cr Progressive rise in BUN and Cr Stable elevated BUN and Cr Historical clues Positive Hx for acute kidney injury etiology ( eg , recent streptococcal infection Hx of chronic hypertension Growth Normal growth Impaired growth Bone status Normal bones Evidence of renal osteodystrophy: Hx of fractures Hematocrit Anemia usually mild Anemia usually severe Kidney ultrasound Normal or enlarged kidney size Small, shrunken kidneys

23. Follow-up Evaluate patients 3 months after AKI for resolution, new onset, or worsening of pre-existing CKD.

24. Prognosis AKI in hospitalized children is associated with increased mortality ICU setting mortality rates associated with AKI are higher: up to 30 to 44% Highest mortality rates are seen in infants, patients with multiorgan failure and those on renal replacement therapy (KRT) Children with AKI are at long-term risk for developing CKD Patients with moderate to severe AKI should be followed annually to detect signs of CKD ( eg , hypertension and proteinuria).