PEDIATRIC ACUTE KIDNEY INJURY

1. PEDIATRIC ACUTE KIDNEY INJURY Sunee Panombualert, M.D. Department of Peditric, Faculty of Medicine, Khon Kaen University, Thailand

2. Outline Diagnosis and definitions of AKI Evaluation of causes of AKI Management of AKI Fluid resuscitate Blood pressure management Diuretics Nutrition Renal replacement therapy

3. Acute kidney injury (AKI) Previously called acute renal failure Rapid (over hours to days) and usually reversible decline in GFR Acute, impairment of kidney function, manifest by changes in urine output and blood chemistries, portend serious clinical consequences

4. AKI definitions AKI is defined as any of the following: • Increase in SCr by > 0.3 mg/dl within 48 hours or • Increase in SCr to > 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.

5. Staging of AKI

6. Normal serum Creatinine(Cr) The Harriet lane handbook 19th edition

7. ESTIMATED CREATININE CLEARANCE eGFR / eCrCl = 0.413 x Ht (cm) Cr (mg/dl) (ml/min/1.73m2) Pediatrics 1976;58:259-263. J Am Soc Nephrol 2009;20:629-637.

8. Evaluation of Kidney Function in the Acute Care Setting Case: You are asked to see a 5-year-old boy with PUV and known chronic kidney disease (CKD; baseline Scr 2.0 mg/dL) who is admitted with urosepsis. Admission Scr concentration was 2.3 mg/dL and increased to 2.6 mg/dL the following day. Question 1: Which statement regarding his kidney function is correct? • Using the MDRD (Modification of Diet in Renal Disease) Study equation, his estimated GFR (eGFR) is 34 mL/min/ 1.73 m2 • Use of the CKD-EPI (CKD Epidemiology Collaboration) equation is more appropriate for this patient, and his eGFR is 32 mL/min/1.73 m2 • Using the Cockcroft-Gault formula, his creatinine clearance is 20 to 32 mL/min • His eGFR cannot be calculated because his Scr concentration is not stable

9. Evaluation of causes of AKI 1. Decreased kidney perfusion (pre-renal states) 2. Intra-renal causes 3. Post-renal causes (obstructive uropathy) 1 2 3 Lancet 2005365:418.

10. Lancet 2005365:418.

11. Decreased kidney perfusion (pre-renal states) • Hypovolemia : Increased losses (hemorrhage, burns, massive vomiting or diarrhea), poor oral intake • Reduced cardiac output : Heart failure, cardiac tamponade, massive pulmonary embolism • Renal vasomodulation/shunting : Medications (NSAID, ACEi/ARB, cyclosporine, iodinated contrast), hypercalcemia, hepatorenal syndrome, abdominal compartment syndrome • Systemic vasodilation : Sepsis, SIRS, hepatorenal syndrome

12. Lancet 2005365:418.

13. Intra-renal causes • Glomerular: • Rapidly progressive (crescentic) GN: anti–glomerular basement membrane • immune complex diseases: IgA nephropathy, postinfectious, lupus, mixed cryoglobuminemia with MPGN • pauciimmuneglomerulonephritis:ANCA-associatedvasculitides:GPA,MPA,EGPA(Churg-Strauss) • ANCA-negative • nephrotic-range proteinuria with associated AKI: HIV-associated nephropathy (secondary FSGS) • Other causes of nephrotic-range proteinuria that commonly associate with AKI:minimalchangediseasewithATN/AIN • Membranous nephropathy+crescenticGNorrenal vein thrombosis; myeloma +multiple different pathologies, but in particular light chain cast nephropathy

14. Acute glomerulonephritis: APSGN Lupus nephritis HSP Ig A nephropathy

15. Tubulo-interstitium • AIN: medications, infection, lymphoproliferative disease • Pigment nephropathy: rhabdomyolysis (myoglobin), massive hemolysis (hemoglobin) • Crystal nephropathy: uric acid (tumor lysis), acyclovir, sulfonamides, protease inhibitors (indinavir, azatanavir), methotrexate, ethylene glycol, acute phosphate nephropathy, oxalate nephropathy, myeloma-associated AKI (cast nephropathy) • ATN: ischemia (shock, sepsis), inflammatory (sepsis, burns), medications • Osmotic nephrosis in setting of sucrose, mannitol and hydroxyethyl starch use

16. Tubule Acute tubular necrosis: • Ischemic ATN • Nephrotoxic ATN

17. Intrinsic renal disease Acute tubular necrosis Ischemic ATN : shock, post cardiac arrest, severe hypoxia, prolong dehydration Nephrotoxic ATN: Exogenous : antibiotic, radio contrast agents, cisplatin,heavy metals Endogenous : Intratubular pigment: hemoglobin,myoglobin Intratubular crystals: uric acid, oxalate Lancet 2005365:418.

18. Medications Commonly Associated With ATN • Aminoglycosides (tobramycin, gentamycin) • NSAIDs (ibuprofen, naproxen, celecoxib) • ACEI (captopril, lisinopril, benazepril, ramipril) • ARB (losartan, valsartan, candesartan, irbesartan) • Amphotericin • Cisplatin • Foscarnet • Iodinated contrast • Pentamidine • Tenofovir • Zolendronic acid

19. Interstitial Acute interstitial nephritis: Drug- associated Infection

20. Vascular Vascular: Vasculitis HUS

21. Intra-renal causes • Vascular: Renal artery stenosis, arterial/venous cross-clamping • Microvascular: Thrombotic microangiopathies (TTP, HUS, aHUS, DIC, APS, malignant hypertension, scleroderma renal crisis, preeclampsia/HELLP syndrome, drug-induced), cholesterol emboli

22. Lancet 2005365:418.

23. Post-renal causes • Bladder outlet: Posterior urethral valve • Ureteral: Bilateral obstruction (or unilateral with one kidney): stones, malignancy, retroperitoneal fibrosis • Renal pelvis: Papillary necrosis (NSAIDs), stones

24. Post- renal injury Stone Posterior urethral valve Tumor Lancet 2005365:418.

25. Acute kidney injury Post renal Intrinsic Pre-renal AGN ATN AIN Vascular Ischemic ATN Nephrotoxic ATN

26. Approach AKI

27. FE Na(%) = U Na/S Na * 100 U Cr/ S Cr FE Urea(%)=U urea/S urea *100 U Cr/ S Cr

28. Laboratory assessment in AKI • Blood : BUN/Cr, electrolyte, Ca, PO4, uric, CBC • Urine : UA, urea, Na, Cr • FE Na(%) = U Na / S Na * 100 U Cr/ S Cr • FE Urea(%)= U urea / S urea *100 U Cr/ S Cr Pre-renal: < 1% ATN: > 2% Pre-renal: < 35% ATN: > 50%

29. Pediatric nephrology, 5th edition

30. Pediatric nephrology, 5th edition

31. Pediatric nephrology, 5theditionC

33. Glomerulonephritis Normal Abnormal glomerular function Decrease GFR

35. Eosinophiluria

36. Management of AKI

37. Management : Fluid Pre-renal: Fluid loss : fluid rehydration, blood transfusion Heart failure : fluid restriction, inotropic drug, diuretics Intrinsic renal cause: AGN: fluid & salt restriction, diuretic(furosemide) ATN: Depends on phase of ATN

38. Clinical course : ATN 3 Phases of ATN Oliguric phase : 1-2 weeks Diuretic phase : replace urine ml/ml Recovery phase Pediatric nephrology, 6th edition

39. Acute tubular necrosis

40. Fluid management : oliguria Restrict fluid = ISL+ urine output + ongoing loss Diuretic change oliguric to non-oliguric phase GI loss CSF Third space loss Insensible water loss = • 300-400 ml/m2/day • 30-40 ml/kg in neonate Pediatric nephrology, 6th edition

41. Management : post-renal AKI Correct obstruction After release obstruction Post-obstructive diuresis Close observe vital signs, urine output Replace fluid & electrolyte

42. Electrolyte and acid-base balance Hyponatremia: fluid restriction, symptomatic  3% NaCl Hyperkalemia: Kayexalate or Kalimate,bicarbonate, insulin+glucose,beta2-agonist Hyperphosphatemia: PO4-binder(CaCO3),restrict PO4, avoid aluminum containing compounds Hypocalcemia : calcium supplement Metabolic acidosis:7.5%NaHCO3,sodamint Pediatric nephrology, 6th edition

43. Management hyperkalemia • Monitor ECG : if change10%calcium gluconate • Decrease K intake/ remove cause : low K diet, off aldactone, ACEI • Shift of K from extracellular to intracellular compartment : NaHCO3, insulin, salbutamol • Remove K from body • Ca+/Na+ polystyrene sulfonate • Furosemide diuretic • Dialysis

46. Dialysis indications • Fluid overload • Symptoms of uremia • Severe hyperkalemia • Severe metabolic acidosis • Severe hyperphosphatemia (especially if accompanied by hypocalcemia) • Prevention or treatment of tumor lysis syndrome and removal of toxins (ingestions or inborn errors of metabolism)

47. Mode of dialysis Hemodialysis Peritoneal dialysis CRRT (Continuous Renal Replacement Therapy)

48. Hemodialysis

49. Peritoneal dialysis

50. CRRT