ACUTE RENAL FAILURE Academic Half Day February 9, 2012
Objectives To review: • the etiologies of acute kidney injury (AKI) in the pediatric population • the work-up/diagnosis of AKI • the management of AKI • What is AKIs? “abrupt reduction in kidney function as measured by a rapid decline in GFR” • Previously known as Acute Renal Failure • Now failure represents one end of the spectrum • Etiology is variable • Definitions/classifications have varied in the literature…
Classification - pRIFLE U/O <0.5cc/kg/h x 8h Risk Injury Failure Loss End-stage eCCl dec 25% eCCl dec 50% U/O <0.5cc/kg/h x 16h eCCl dec 75%/ < 35ml/min/1.73m2 <0.3cc/kg/h x 24h/ Anuric x 12h Persistent failure >4wks Failure > 3 months
Leads to: • Impaired excretion of nitrogenous waste • Impaired water and electrolyte balancing • Impaired acid/base regulation • Impaired vascular tone regulation
Burden of disease Incidence (US): 0.8/100 000; ~1/10 in ICU • Increasing Independent risk factor for ICU mortality Increases length of hospital stay May lead to chronic renal failure (40-50% ICU)
Etiologies: a general approach Though likely multifactorial, can be divided into: Pre-renal Renal Post-renal
Volume deplete: GI Vomiting Diarrhea Bleeding Trauma Surgery Diuresis Diabetes - DM, DI Drugs Kidney sees less volume: Sepsis CHF Cirrhosis Vascular - also consider in renal RAS Thrombus Takayasu, PAN, KD Drugs NSAIDs ACEi ARBs Pre-renal causes:Any cause which results from kidney seeing to little blood flow
Renal causes Vascular: Microvasculature: • Sickle cell disease • HUS • Tumour lysis • rhabdomyolysis ?Syndromes • Hepatorenal • Cardiorenal • Pulmonary-renal • Glomerular: • Glomerulonephritis: • Post-infectious • membranoproliferative • SLE • HSP Tubulo/Interstitial:Acute tubular necrosis -secondary to nephrotoxic insults or poor perfusion Acute interstitial nephritis -drugs -infxn Cortical dysplasia -hypoxia/ischemia->infarct -toxins/severe HUS ?Sepsis inflamm, not all volume related
Hemolytic UremicSyndrome History of Ecoli, Shigella, shiga-toxin… Atypical (non-diarrhea, non-shiga-toxin) Hemolytic anemia with fragmented RBCs Thrombocytopenia Renal injury CNS, liver, pancreas can also be affected
Post-infectious glomerulonephritis Occurs in ages 5-12, post-GAS. Presentation can be asymptomatic to nephritis complete with gross hematuria, proteinuria, HTN, edema Labs: abnormal urinalysis, low complement Rx: supportive. Prognosis: most make complete recovery.
HSP -Causes renal issues d/t IgA deposition. -A/W palpable purpura, arthritis, abdo pain. -Renal more likely to be an issue in older kids -Rx: if crescenteric, GN - steroids. -prognosis: often relapses. Can have late deterioration even if full recovery. 10-30% adults go on to have end-stage disease.
Acute TubularNecrosis Describes an end effect of tubular damage… • Secondary to perfusion insults • Secondary to toxins Change in blood flow, obstruction and passive filtrate backflow into tubular cells can cause a cycle leading to further death…
AIN Drugs (71%) - 1/3 antibiotics • Penicillins, cephalosporins, NSAIDs, sulfonamides, cipro, rifampin, PPIs, allopurinol… and more Infection (15%) • Strep, Legionella, leptospirosis, CMV, EBV… many Tubulointersitial nephritis and uveitis (5%) Autoimmune: SLE, Sjogren’s Sarcoidosis Idiopathic (8%)
Nephrotoxins Vascular effect • ACEi, cyclosporine, tacrolimus Tubular effect • Proximal: aminoglycosides, amphotericin B, cisplatin, immunoglobulins, contrast • Distal: NSAIDs, ACEi, lithium, cyclophosphamide • Obstruction: sulfa, acylovir, methotrexate AIN
Post-renal causes Two kidneys - distal or bilateral proximal obstruction Single kidney - obstruction anywhere • Posterior urethral valves • Ureteropelvic junction obstruction • Ureterovesicular junction obstruction • Ureterocele • Stones • Tumour • Hemorrhagic cystitis • Neurogenic bladder
On history… ? pre-renal: • Vomiting, diarrhea, bleeding, sepsis, dec PO • Drug use - inc NSAIDs ? renal: • Bloody diarrhea? (HUS) Recent illness? (PSGN) Crush injury? • Drug use: aminoglycosides, antifungals, chemo • Associated lung/heart/liver symptoms? (dual organ) ? post-renal:
On physical… Pre-renal: • Dehydration • Signs of heart failure/cirrhosis/sepsis Renal: • Edema (nephrotic syndrome) • Purpura (HSP Post-renal: palpable bladder?
What to order? BUN, Cr, lytes, fractional excretion of sodium Urinalysis
NORMAL: -pre-renal (may be concentrated) -post-renal -ATN ABNORMAL: -brown granular/epithelial casts = ATN -red cell casts = glomerulonephritis -proteinuria = glomerular -pyuria, white cell casts = UTI or glomerulonephritis (post- infxn) -hematuria = AIN, vasculitis, infarction, obstruction On labs… Everyone gets a urinalysis…
And even more information from urine… Urine osmolality: • Typically low in ATN (<350 mosmol/kg) • Typically high in pre-renal disease (>500) Urine volume: Often low, especially given criteria for AKI. However, some ATN is non-oliguric Urine eosinophils Urine sodium…
Sodium excretion Why? Helps distinguish pre-renal vs ATN… • >30-40 mEq/L = ATN • <10 mEq/L = effective volume depletion(20-30 in infants) • BUT what if there is a large urine output?
Fractional Excretion of Sodium FENa compensates for the urine output… UNa x PCr PNa x UCr …can also be thought of as UNa/PNa UCr/PCr <1% --> pre-renal disease 1-2% --> ?? >2% --> ATN
Bloodwork… CBC: look for MAHA, thrombocytopenia Extended lytes. Renal injury can result in: • Hyperkalemia • Hyperphosphatemia • Hypocalcemia • Metabolic acidosis Other options, depending on history: ANCA, ANA, ASOT, complement, drug levels…
And of course, creatinine Creatinine is usually elevated • Normal Cr varies by age • Note Cr can NOT be used to estimate GFR in acute kidney injury… • This is why the search is on for a “troponin of the kidneys”
Troponin of the kidneys? Unfortunately, not yet… Some ideas: • Urinary neutrophil gelatinase-associated lipocalin (NGAL) • Increased 50-fold, and 24h before serum Cr • Has been shown to predict AKI severity in SLE, HUS, renal transplant patients • Kidney injury molecule - 1 (KIM-1) • IL-18
Imaging Ultrasound - in all children if etiology unclear • # of kidneys • Size of kidneys • Obvious parenchymal damage • Obstruction • Thrombus/vessel occlusion
Renal biopsy Only when diagnosis remains unknown, or there is a failure to respond to treatment
Treatment Principles: • FEN • Avoid complications • Treat underlying cause Generally pediatric nephrology will be involved.
Child can be hypo-, eu- or hypervolemic. FEN - fluids HTN can occur and is usually secondary to volume overload. Treatment based on diuretic response, severity.
FEN - electrolytes Hyperkalemia - if severe (>7) - C BIG K Die… • Don’t give K (IVs, low K diet) • stabilize the cardiac membrane - IV calcium gluconate • Move K ECF -> ICF by: • Insulin (with glucose) • Sodium bicarb • Beta agonists • Remove K from the body - kayexalate • Can try diuretics - unlikely to do enough • RRT if the above doesn’t work
FEN - electrolytes Acidosis • Respiratory compensation can be enough • Sodium bicarb ONLY if life-threatening and/or contributing to hyperkalemia • Def not if pH >7.2 or bicarb >14mEq/L • Can decrease Ca further -> seizures • Can increase intravascular volume • If refractory volume overload, hypernatremia -> RRT
FEN - electrolytes Hyperphosphatemia: • Low phosphate diet • Binders Hypocalcemia: • Calcium gluconate • Can pre-empt if sodium bicarb being given
FEN - Nutrition AKI is a catabolic state Ensure adequate calories - 120kcal/kg/d in infants - usual maintenance for children PO -> enteral -> TPN If fluid balance off with adequate nutrition: RRT
Avoid complications Including making things worse…so no: Aminoglycosides NSAIDs Antifungals Immunosuppressive drugs Contrast media
Renal Replacement Therapy (RRT) Indications: • Uremia s/s - pericarditis, neuropathy, decline • Azotemia - BUN >36 • Refractory fluid overload - HTN, pulm edema, CHF • Refractory hyperK, hypo/hyperNa, acidosis • Nutritional support with fluid balance issues
RRT Options: Continuous renal replacement therapy Peritoneal dialysis Hemodialysis
Prognosis Mortality: 60% (critically ill) 20-25% go on to have some degree of chronic renal issues
Take home points Etiology: Best divided into pre-, renal and post-renal Work-up: Urinalysis, ultrasound, bloodwork… Treatment: Fluids - close balance Electrolytes - esp K, PO4, Ca Acidosis Nutrition Dialysis - talk later today
References Akcan-Arikan A, Zappitelli M, Loftis L, Washburn K, Jerrerson L, and Goldstein S. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney International; 2007: 71: 1028-35. Basu R, Devarajan P, Wong H, and Wheeler S. An update and review of acute kidney injury in pediatrics. Pediatric Critical Care Medicine; 2011: 12(3): 339-47. Imam A. Clinical presentation, evaluation, and diagnosis of acute kidney injury (acute renal failure) in children. Uptodate. Accessed Feb 8, 2012 at http://www.uptodate.com.ezproxy.lib.ucalgary.ca/contents/clinical-presentation-evaluation-and-diagnosis-of-acute-kidney-injury-acute-renal-failure-in-children?source=search_result&search=acute+kidney+injury&selectedTitle=2~150 Imam A. Prevention and management of acute kidney injury (acute renal failure) in children. Uptodate. Accessed Feb 8, 2012 at http://www.uptodate.com.ezproxy.lib.ucalgary.ca/contents/prevention-and-management-of-acute-kidney-injury-acute-renal-failure-in-children?source=search_result&search=acute+kidney+injury&selectedTitle=1~150 Kliegman R, Stanton B, Geme J, Schor N, and Behrman R. Nelson Textbook of Pediatrics 19th e. Elsevier; 2011: 1814-22.