Professor and Director. Children s Hospital of Richmond

Transcription

1 Evaluation of AKI in term and premature infants Timothy E. Bunchman Professor and Director Pediatric Nephrology & Transplantation Children s Hospital of Richmond Virginia Commonwealth Univ. School of Medicine Timothy.bunchman@vcuhealth.org pedscrrt@gmail.com

2 Thank you to Cherry Mammen MD, FRCPC, MHSc Pediatric Nephrologist, BC Children s Hospital IPNA for support of this conference

3 Learning Objectives Defining AKI in this population Factors that may influence AKI management in this population

4 AKI: Definition and Diagnosis Abrupt reduction in GFR Differential diagnosis includes: Pre-renal Volume depletion; cardiac dysfunction Renal Vascular; glomerular; tubular; interstitial Post-renal Obstruction Complex, multi-factorial physiology

5 Neonatal AKI: Special Challenges Specific stresses unique to the neonate Different renal physiology in newborn Risks associated with neonatal illness and its treatment Low birth weight; fluid loss; infection; drugs Our ignorance of details in neonatal AKI Do we really know which babies have AKI?

6 Neonatal AKI Definition (modified KDIGO criteria)

7 244 Neonatologists (73% US based) & 131 Nephrologists (75% US based) Based on 3 NICU cases scenarios representing KDIGO AKI Stages 1, 2, & 3 98% of nephrologists vs 51% of neonatologists were aware of published neonatal AKI definitions Stage 1: 62% of neonatologists diagnosed AKI Stage 2: 76% of neonatologists diagnosed AKI Stage 3: 99% of neonatologists diagnosed AKI Kent AL et al. Am J Perinatol 2017

8 Challenges with serum creatinine Marker of function (not injury) Rises late (24-48 hrs after initial injury) Rises once 25-50% of renal function is lost Does not differentiate the nature & timing of injury Affected by fluid status (dilution from fluid overload) AKI incidence/staging changes when corrected for fluid overload Type of measurement (Enzymatic vs Jaffe) Jaffe method Interference with albumin & bilirubin May overestimate Cr (0.2 mg/dl in ELBW infants) Basu RK et al. Pediatr Crit Care Med 2013 Allegaert K et al. J of Maternal-Fetal & Neonatal Med 2012

9 Issues with creatinine (NICU) Interference with maternal creatinine Highly dynamic GFR in 1 st few weeks of life Low muscle mass population Frequency of Cr monitoring varies from NICU to NICU What threshold of Cr rise should we use? Historically, absolute SCr >1.5-2 mg/dl has been used Are these thresholds too strict? Are we missing too many cases with milder injury? Should we be using lower % SCr thresholds (prifle, AKIN, KDIGO)?

10 Neonatal serum creatinine trends Is this AKI?

11 Creatinine trends (premature infants) Divided by levels by gestational age Is this AKI??Tubular reabsorption of SCr 100 umol/l= 1.1 mg/dl 120 umol/l = 1.35 mg/dl Gallini F Pediatr Nephrol 2000 Guignard JP Pediatrics 1999

12 Urine output issues What is the definition of oliguria in a neonate? Minimum urine output 1 cc/kg/hr to remain in solute balance Most standardized definitions define oliguria <0.5 cc/kg/hr How do we measure U/O accurately? Many NICU patients do not have Foley catheters How do we deal with the poop situation & combos on flow sheets? When do we start the urine output clock in NICU pts? Many infants do not urinate right away Does adding U/O criteria change AKI incidence/staging?

13 24 hours good time to start the clock? Clark DA.

14 Retrospective NICU study (312 infants) 48% pre-term, 24% 5-min APGAR <7 Overall mortality 12.8% U/O measured by weighing diapers q3hours AKI defined by prifle (egfr & U/O criteria)

15 Patients divided into U/O thresholds (excluding 1 st 24 hrs of life) Group 1: >1.5 cc/kg/hr x 24 hrs Group 2: cc/kg/hr x 24 hrs Group 3: cc/kg/hr x 24 hrs Group 4: <0.7 cc/kg/hr x 24 hrs Bezerra CTM et al. Nephrol Dial Transplant 2013

16 Bezerra CTM et al. Nephrol Dial Transplant 2013

17 Bezerra CTM et al. Nephrol Dial Transplant 2013 prifle criteria: AUC for mortality 0.689, addition of proposed U/O criteria 0.885

18 Adding U/O Criteria Changes Incidence Jetton J et al. The Lancet (Child- Adolescent) 2017

19 Neonatal AKI Biomarkers

20 Published norms for premature infants without AKI

21 AKI biomarkers in premature infants during first week of life Table 5. Performance for biomarker value to acute kidney injury (maximum biomarker level for all, except those shown with ** which are minimum values) *GA Adjusted (pg/ml) Ideal crude cutoff *Crude AUC AUC Albumin CystatinC EGF** NGAL OPN UMOD** Clusterin α-gst * log transformed before analysis to normalize the distribution. Askenazi D et al. CJASN 2016

22 Cystatin C vs Serum Creatinine Advantages of Cystatin C Independent of age, sex, weight, height Minimal amounts cross placenta Filtered by glomerulus, completely reabsorbed, & not secreted However, 5x the cost of SCr ($3-5/assay) Single center cross-sectional study 60 preterm (<37 wks) & 40 full term infants enrolled SCr measured by enzymatic method after 1 st 48 hours along with serum CysC egfr calculated with various pediatric estimating equations (Cr & cystatin-based) Compared with inulin clearance values taken from literature (7 studies) Abitbol CL et al. J Peds 2014

23 Cystatin C vs Serum Creatinine SCr based equations underestimated inulin GFR by >20% Seen at all gestational ages Cystatin C is superior to SCr in neonates in estimating GFR Abitbol CL et al. J Peds 2014

24 AWAKEN Assessment Worldwide Acute Kidney Epidemiology Neonates Published on September 7 th, 2017 Lancet: Child and Adolescents - online first

25 AWAKEN methods Multi-center retrospective cohort study 24 level 2-4 NICUs All NICU admissions from Jan 1 March 31, 201 Inclusion criteria Admission during the study period Provision of at least 48 hours of IV fluids

26 Exclusion criteria AWAKEN methods Admission at > 2 weeks of life Newborns requiring congenital heart disease repair < 7 days o life Death within 48 hours of admission Lethal chromosomal anomaly Severe, bilateral congenital kidney and urinary tract disease

27 AWAKEN: Breakdown of Screened vs. Enrolled

28 AKI Incidence in AWAKEN study No AKI AKI

29 AKI Incidence by GA

30 AKI incidence by GA No AKI AKI

31 AKI Incidence by GA No AKI AKI

32 AKI Incidence by GA No AKI AKI

33 Risk Factors for Neonatal AKI Very low birthweight Congenital Heart Dz Cardiac bypass ECMO The depressed or asphyxiated infant Renal anomalies (CAKUT) Hypotension or hypoperfusion Infection/sepsis Drugs Umbilical catheterization Multi-organ disease

34 We have known this for a while...

35 AKI After Congenital Heart Surgery 430 infants <90 days (median 7d) 34w term Median weight 3.1kg Heart surgery for congenital defects Blinder et al. J Thorac Cardiovasc Surg 2012

36 AKI After Congenital Heart Surgery No AKI 48% PostOp AKI 52% PostOp AKI: N= Stage 1 59 Stage 2 31 Stage 3 Blinder et al. J Thorac Cardiovasc Surg 2012

37 Neonatal AKI from Nephrotoxin Exposure 107 VLBW infants over 1 year ( ) 93 (87%) exposed to at least one nephrotoxic medication Mean number of meds: 1.64 Median number of meds: 2 AKI rate in study: 28/107 (26%) All were exposed to nephrotoxic meds; those without nephrotoxins did not get AKI Rhone et al. J Matern Fetal Neo Med 2014

38 Evaluation of the infant What is their volume status and perfusion? Are they receiving nephrotoxic agents? What does their imaging show?

39 Management of Established AKI: Pharmacotherapy Attempted Therapies Diuretics Mannitol Dopamine Fenoldopam Glucocorticoids Atrial natriuretic peptide N-acetylcysteine (other than contrast-induced AKI Definitive Therapies Theophylline Uric acid manipulation

40 Conclusion As you can see the definition of AKI is not clear But The evaluation of AKI and management is consistent with that of older children

41 Conclusion Pay attention of risk factors that cause or contribute to (new or ongoing) AKI Perfusion and volume status Are they obstructed (imaging) Are they receiving nephrotoxic agents

42 Thank you Contains all talks given at the PCRRT meetings from 2000 to the most recent in 2017