pediatric acute kidney injury (aki)课件

Pediatric Acute Kidney Injury (AKI),Heather Stewart, MD Internal Medicine-Pediatrics Nephrology Fellow UNC Kidney Center September 13, 2010,AKI,Formerly referred to as acute renal failure Abrupt reduction in kidney function measured by decline in GFR Results in disturbances Impaired nitrogenous waste excretion Loss of H2O & electrolyte regulation Loss of acid-base regulation Contributing factor in morbidity & mortality of critically ill,A Common, Serious Problem,Present in 5% of all hospitalized patients, & up to 30% of ICU patients Incidence is increasing at an alarming rate Mortality rate 50% in dialyzed ICU patients 25% of ICU dialysis survivors progress to ESKD within 3 years,Clinical Approach to AKI: Pre-, Intra-, and Post-Renal,History Volume status Ultrasound Urinalysis,US shows Hydronephrosis,Post-Renal,Urinalysis Normal,Urinalysis Abnormal,Tubulointerstial Disorders,Glomerular and Vascular Disorders,Pre-renal,Nephrologists Clinical Approach to AKI,History Volume Status Ultrasound Urinalysis,Hydronephrosis,Post-Renal,Prostate disease BPH Cancer Pelvic malignancy Stones Stricture Retroperitoneal fibrosis,Normal Urinalysis,Pre-Renal,Low ECF Volume GI losses Hemorrhage Diuretics Osmotic diuresis,Altered renal blood flow or hemodynamics Sepsis Heart failure Cirrhosis/Hepatorenal syndrome Hypercalcemia Medications NSAIDs/Cox-2 inhibitors ACE inhibitors Angiotensin II receptor blockers Vascular disease,Vascular Disorders,Tubulointerstitial Disorders,Glomerular Disorders,Tubular obstruction Crystals Calcium oxalate (Ethylene glycol, orlistat) Indinivir Acyclovir Methotrexate Tumor lysis syndrome Myeloma cast nephropathy,Acute tubular necrosis Ischemic Nephrotoxic Contrast-induced Rhabdomyolysis,Acute interstitial nephritis Medication-induced Autoimmune Sjogren syndrome Sarcoidosis Infection-related,Arterial Renal artery stenosis Renal artery thromboembolism Fibromuscular dysplasia Takayasu arteritis Medium vessel Polyarteritis nodosa Kawasaki disease Small vessel Glomerulonephritis Thrombotic microangiopathies Cholesterol emboli Renal vein Renal vein thrombosis Abdominal compartment syndrome,Renal parenchymal disorders,Abnormal urinalysis,Pathophysiology: Newborn,Embryogenesis completed by 35th wk resulting in 0.6-1.2 million nephrons per kidney Immaturity limits kidney fxn Hemodynamic changes birth Increased risk of hypovolemia b/c lg insens. losses,Pathophysiology: Newborn,RBF increases after birth b/c renal vasc resist decreases & systemic BP increases As a proportion of CO, RBF inc from 2 to 4% in fetus 1wk of life 10% adult 20% Dec ability to compensate for significant hemodynamic changes,Pathophysiology: Newborn,Limited Urine concentrating ability Concentration inc from 400 mosm/kg in 1st few days to 1200 mosm/kg at 1yr of age Low CM solute gradient Decreased cAMP in response to ADH Short Loop of Henle Interference by PGs Inc risk of volume depletion,Epidemiology,Retrospective review est. a yearly incidence for AKI 0.8 /100,000 This is about 1/5 of that seen in adults Incidence rising with inc availability of advanced technology Txplt: BM, Liver, Heart CHD surgery Care of VLBW infants,Etiology: Newborn,Perinatal asphyxia Prerenal Dz & ATN Renal Vasc Thrombosis RAT RVT Nephrotoxins Urological abnormalities,Etiology: Newborn,Perinatal asphyxia Most common cause Diminished RBF due to hypovol/hypotension Preglomerular vasoconstriction Increased catechols, adenosine, & angiotensin Postglomerular vasodilatation dec GFR Activated RAAS and inc ADH salt & H20 retention with oliguria,Etiology: Newborn,Renal Vascular Thrombosis RAT Assoc with UAC placement Thrombi can partially occlude abd Ao thus dec renal perfusion embolize to renal artery = infarction hematuria (gross or micro) Thrombocytopenia, anemia, leucocytosis, DIC,Etiology: Newborn,Renal & Urinary Tract Abnml Polycystic kidney disease AD (1:4001:1000) or AR Multicystic Dysplastic kidneys Renal agenesis Bilateral (1 in 4000) Potter Sequence Unilateral (1 in 550) inc incidence of Mullerian duct defects Urinary tract obstruction bilat/unilat hydro PUV Severe UPJ,Etiology: Children,Volume depletion Bleeding, GI, burns Heart failure, shock, *cirrhosis Dec effective circulating volume Vascular RAT, RVT, HUS, *Vasculitis *Glomerular Nephrotoxins/AIN Urologic abnormalities,Presentation: Newborn,History: Prenatal conditions oligo- or polyhydramnios; renal abnml noted on antenatal US; and antenatal medications Neonatal conditions prematurity, perinatal asphyxia, RDS, sepsis, UAC, Rx administration, volume depletion, delayed 1st UOP, abnml urine stream in males PxEx: Edema, BP, enlarged/absent kidneys, distended bladder, dysmophic features (myelomeningocele, anal atresia, PBS, facial/limb deformities),Presentation: Newborn,Oligoanuria No UOP by 48hrs of age or dec UOP (less than 1 ml/kg/hr) Elevated Cr 1.5mg/dL or increasing by at least 0.2-0.3 mg/dL per day Azotemia BUN 50mg/dL Lab abnmls hypoNa, hyperK, met acidosis, hyperPhos, hypoCa,Presentation: Children,History: AGE, hemorrhage, sepsis, decreased oral intake Bloody diarrhea w/ oliguria (500ml/1.73m2/day) or anuria HUS Pharyngitis or impetigo PIGN Hemoptysis and renal impairment Pulm-Renal Syndrome (Wegners, Goodpastures) Trauma/crush injury rhabdomyolysis Exposure to nephrotoxins aminoglycosides, amphotericin-B, chemotherapy Rx PxEx: Tachycardia, dry MM, sunken eyes/fontanel, orthostatic BP, decreased skin turgor Edema nephrotic syndrome, heart failure, liver failure Skin findings purpura, petechiae, malar rash, maculopapular HSP/SLE, AIN,Common Nephrotoxic Agents,Antimicrobial agents Aminoglycosides Amphotericin B Acyclovir Foscarnet Pentamidine Chemotherapeutic agents Cisplatin Mitomycin C Streptozocin,Vasoactive drugs NSAIDS ACE inhibitors CSA, Tacrolimus, Rapamycin Radiocontrast agents Colloidal agents Dextran 40 Hydroxyethyl starch,Diagnosis of AKI is Often Delayed,Elevation in serum Cr - current gold standard Normal serum Cr varies widely with age, gender, diet, muscle mass/metabolism, medications (Bactrim, Cimetidine), and hydration status Serum Cr can take several days to reach a new steady state Up to 50% of kidney function may be lost before serum Cr even begins to rise,Evaluation,Serum chemistries Na, K, CO2, Cr, Ca, Phos, Albumin CBC Polycythemia or thrombocytopenia = RVT Microangiopathic hemolytic anemia assoc with thrombocytopenia = HUS Eosinophilia = AIN Urine Urinalysis with microscopy Urine lytes (Na, Cr, Urea in Lasix use) Other Aminoglycoside levels Uric acid if TLS suspected C3, C4, dsDNA, ANA, ANCA, ASO,Evaluation,Renal Imaging RUS: 1 or 2 kidneys, echogenicity, renal size, obstruction VCUG: to assess for obstructive uropathy +/- VUR in newborns wit h renal anomalies,Evaluation: Serum Creatinine,Normal ranges: Newborn 0.3-1.0 mg/dL Declines to infant values* - 1wk in term infants & 2-3wks in preterm infants *Infant 0.2-0.5 mg/dL Child 0.3-0.7 mg/dL Adolescent 0.5-1.0 mg/dL Even if value remains in normal range a sequential inc in Cr concentration strongly suggests a dec in GFR. Certain Rx Cimetidine, Bactrim Renal dosing in AKI assume eGFR 15 ml/min/1.73m2,AKI,Indices Pre-Renal ATN UNa Children 10 Neonates 30 Spec Grav 1.018 40 2% Neonates 3% * low FeNa not unique to Pre-renal nml tub fxn but low GFR like acute GN, vasculitis, acute obstruction Urine Osmolality 500 350 Sediment normal active,Urinalysis,Urine Sediment,Monomorphic RBCs,Dysmorphic RBCs,Hyaline cast,RBC cast,Urine Sediment,RTE cast,Fatty cast,ATN,WBC cast,Management,Fluids Hyperkalemia Metabolic Acidosis Hypocalcemia & hyperphosphatemia Hyponatremia Nutrition Hypertension,Management: Intravascular Volume Fluids,Place foley catheter Fluid challenge - Isotonic saline 10-20 ml/kg (+) response ( 1ml/kg/hr) indicates pre-renal cause (-) response indicates intrinsic cause Prevent fluid overload - restrict D5W or D10W with bicarbonate to replace insensible losses (approx 1/3 of maintenance) Replace urine losses with NS Lasix (1-5mg/kg) for signs of overload Discontinue fluids/TPN with K,Management: Intravascular Volume Diuretics,Loop - Bolus vs Drip Bolus short onset of duration of action Multiple doses (if not effective) likely to cause ototoxicity Drip Continuous superior to bolus due to metabolism, less drug needed (Martin et al, CCM 1994 22:1323) 26 Post-Op Cardiac Neonates 1mg/kg q4hrs vs 0.1 mg/kg/hr gtt UOP similar but gtt had less drug & more consistent UOP (Luciani et al, Ann Th Sg 1997 64:1133),Management: Intravascular Volume Diuretics,Augmentation of Loop with addition of Thiazide Augment loop diuretics by delivering more Cl to the distal tubule by blunting Na reaborption Fiser et al, Kid Int 1994 46:482 IV thiazide vs Control to augment loop in 10 adults with AKI Thiazide addition resulted in sig improvement in UOP 5mg/kg/dose q6 Diuril followed by Lasix IV q6 or Lasix gtt,Management: Intravascular Volume Albumin good or bad?,Finfer et al, NEJM 2004 350:2247 7000 adults with hypovolemia randomized to NS or 4% albumin No difference in AKI or need for dialysis BUT NS group received 1.3 times greater volume to restore hemodynamics Volume excess may be a negative indicator of survival in AKI,Management: Intravascular Volume Dopamine,Renal-dose dopamine (0.5 to 3-5 mcg/kg/min) Increases RBF by promoting vasodilatation & may improve UOP by promoting naituresis Not shown to alter course of renal failure Not proven to convert oliguric to non-oliguric AKI No effect in decreasing need for dialysis or improving survival in patients with AKI Bellomo et al, Lancet 2000 36:2139 RCT that revealed no change in survival b/w Dopamine and placebo Complications: tachycardia, arrhythmias, & myocardial ischemia,Management: Hyperkalemia,“C BIG K Die” Calcium gluconate (from pharmacy) or Calcium chloride (on crash cart) Bicarbonate/beta-agonist (Albuterol) Insulin + Glucose Kayexalate Diuretic (Lasix) EKG changes: peaked T waves, flattened P waves, inc PR interval, widening of QRS, bradycardia, SVT/VT, and Vfib,Management: Hyperkalemia,SP Andreoli, Pediatr Drugs 10:379-390,Management: Acidosis,Impaired acid excretion + increased acid production from underlying condition Administration where max resp compensation is adequate and/or acidosis is contributing to hyperK Plasma bicarb falls below 15 meq/L or arterial pH 7.25,Management: Acidosis,Correction estimated by HCO3 dose = (16-measured HCO3)(0.4)(wgt in kg) Or empirically give HCO3 at dose of 1-2 meg/kg Avoid rapid correction HTN, fluid overload, intracranial hemorrhage If (+) hypoCa correct this 1st b/c HCO3 will decrease ionized Ca tetany or SZ,Management: hypo-Ca, Hyper-Phos, & hypo-Na,hypo-Ca: generally not treated unless symptomatic or hypoCa is severe Hyper-Phos: lowering Phos tends to raise Ca Restrict dietary Phos Use Ca-carbonate for Phos binding hypo-Na: typically assoc from H2O intake that cannot be excreted Restrict free H2O “Hot salt” if Na 120 meq/L & symptoms,Management: HTN,Prevent by avoiding fluid overload Diuretics if responsive Vasodilators usually drug of choice Nitroprusside, Labetalol, or Nicardipine gtt Intermittent IV doses of Hydralazine or If taking po oral minoxadil or hydralazine,Management: Nutrition,AKI assoc w/ marked catabolism Balance of volume and components Enteral preferred (Nepro, RenaCal, etc.) over central Consider the following with TPN Volume High Dextrose, low rates; 20% lipids Components AA 1-1.5 gm/kg No K, Phos,Traditional Indications for Kidney Support in AKI,“AEIOU” Severe metabolic acidosis unresponsive to bicarbonate therapy Electrolyte disturbance despite medical therapy; Refractory or severe hyperkalemia Intoxication/Ingestions (i.e. lithium, ASA) Overload - Diuretic unresponsive hypervolemia Uremic complications pericarditis,Dialysis Modalities,Intermittent hemodialysis Continuous therapies Continuous hemofiltration Continuous hemodialysis Continuous hemodiafiltration Peritoneal dialysis,Dialysis Machines at UNC,Gambro Phoenix Intermit HD,Gambro PrismaFlex Adult CRRT,Gambro Prisma: Peds CRRT,Baxter HomeChoice PD,Dialysis Modalities,SP Andreoli, Pediatr Drugs 10:379-390,Choice of Modality,Influenced by age, size, and medical comorbidities of patient Availability of access placement HD/CRRT are technically challenging in neonates PD preferred in neonates Safe, effective, technically simpler, less expensive Can be initiated after catheter placed & 3days after major abd surgery (i.e. NEC),Timing of Dialysis in AKI,Patients with AKI,Early Dialysis,Late Dialysis,Die without Dialysis,Recover without Dialysis,Timing of CVVH in AKI (adults),N=35,N=36,Bouman CS et al. Crit Care Med. 2002 Oct;30(10):2205-11.,68.8%,75.0%,Adverse Outcomes Associated with RRT,Delay in recovery of kidney function Access related complications Infection Hemorrhage Thrombosis Vascular injury Circuit associated complications Bio-incompatibility Anticoagulation-associated complications,Adverse Outcomes Associated with RRT,Hemodynamic compromise Electrolyte and metabolic complications Errors in compounding fluids Not common here as we use standard dialysate at UNC Acid-base disturbances Thermal balance Electrolyte and nutrient depletion Hypokalemia Hypophosphatemia Vitamins and micronutrients Amino acids,Prognosis,Highly dependent on underlying etiology, age of patient, and clinical presentation AKI neonates (review) Oliguric AKI mortality as high as 60% CHD & Uro abnml mortality up to 86% Children (retrospective) 3 system organ failure assoc with more than 50% mortality,To infinity and beyond . . . although it may be light-years away.,Future developments in the diagnosis of AKI,Need for AKI Biomarker(s),The paucity of early biomarkers has crippled our ability to institute therapy Need early biomarkers for improved understanding, early treatment, and better outcomes,Towards a Kidney Troponin,Multiple therapies 50% Mortality,Supportive Care High Mortality,Urinary Biomarkers,*,*,*,* Released by injured tubular cells * Decreased reabsorption * Released inflammatory mediator,*,*,Urinary Biomarkers,NGAL Covalently bound protein to gelatinase from human neutrophils Expressed in low levels in diverse human tissues Induced in injured tissues including kidney tubular cells Increases in the blood & urine within 2-4 hrs after injury Easily detected in urine,Urinary Biomarkers,Studies Support NGAL as Biomarker of AKI in the following: Pediatric Cardiac Surgery Pediatric Contrast Induced Nephropathy Adult Emergency Room Patients NGAL increases in CKD Better marker in pediatric than adult patients Very stable in the urine Rapid ELISA,Urinary Biomarkers: Clinical Performance,CJASN ePress. Published on August 26, 2010 as doi: 10.2215/CJN.00740110.,Urinary Biomarkers: Clinical Performance,CJASN ePress. Published on August 26, 2010 as doi: 10.2215/CJN.00740110.,Urinary Biomarkers in the Diagnosis of AKI Post-Cardiac Surgery,Han et al. Clin J Am Soc Nephrol 4: 873882, 2009.,Urinary Biomarkers: Confounding Factors,Role of Biomarkers in AKI,Early prediction & diagnosis of AKI (before inc in serum Cr) Identify the primary locationof injury (proximal tubule, distal tubule, interstitium, vasculature) Pinpoint duration (AKI, CKD) and severity Identify the etiology of AKI (ischemic, septic, toxic, combination),Take Home Points,Take Home Points: Prevention,Recognizing whom is at risk Unrecognized CKD in pediatrics as it is “silent” due to interstitial disease assoc with polyuria & tendency for dehydration NPO for procedures Exposure to Nephrotoxins (i.e. NSAIDs, Contrast, Abx, etc.) NAC may be beneficial Bicarb may be beneficial Watch for 2ndry electrolyte changes Met Alk can induce hypo-Ca Close monitoring of serum levels of nephrotoxic drugs Removing vasodilators ahead of time (i.e. ACEi, ARBs) Hydration, Hydration, Hydration - Adequate fluid repletion in hypovolemia Aggressive hydration & alkalinization of urine prior to chemotherapy Preventive therapy for post-ischemic ATN is uproven “Renal-dose” Dopamine, Mannitol, Lasix gtt,Take Home Points: Management,Volume status Hyperkalemia: Therapy “C BIG K Die” Acidosis HTN Nutrition Dialysis: Indications “AEIOU”,Take Home Points: Prognosis,depends on etiology, age of patient, clinical presentation, and status of patient Hypotension & the need for inotropes during dialysis are significant poor predictors for patient survival,Take Home Points: Future Developments,Current clinical tests do not allow early detection of cases at a time when interventions may have the biggest effects Urinary biomarkers under development show great promise of these NGAL is the most advanced Longer term, clinical outcome studies needed to validate utility & validity of AKI biomarkers,Nephrologists Clinical Approach to AKI,History Volume Status Ultrasound Urinalysis,Hydronephrosis,Post-Renal,Prostate disease BPH Cancer Pelvic malignancy Stones Stricture Retroperitoneal fibrosis,Normal Urinalysis,Pre-Renal,Low ECF Volume GI losses Hemorrhage Diuretics Osmotic diuresis,Altered renal blood flow or hemodynamics Sepsis Heart failure Cirrhosis/Hepatorenal syndrome Hypercalcemia Medications NSAIDs/Cox-2 inhibitors ACE inhibitors Angiotensin II receptor blockers Vascular disease,Vascular Disorders,Tubulointerstitial Disorders,Glomerular Disorders,Tubular obstruction Crystals Calcium oxalate (Ethylene glycol, orlistat) Indinivir Acyclovir Methotrexate Tumor lysis syndrome Myeloma cast nephropathy,Acute tubular necrosis Ischemic Nephrotoxic Contrast-induced Rhabdomyolysis,Acute interstitial nephritis Medication-induced Autoimmune Sjogren syndrome Sarcoidosis Infection-related,Arterial Renal artery stenosis Renal artery thromboembolism Fibromuscular dysplasia Takayasu arteritis Medium vessel Polyarteritis nodosa Kawasaki disease Small vessel Glomerulonephritis Thrombotic microangiopathies Cholesterol emboli Renal vein Renal vein thrombosis Abdominal compartment syndrome,