The Journey from AKI to RRT

Loai Eid, MD, MSHS, FAAP, FASPN

Consultant Pediatric Nephrologist

Pediatric Nephrology & Hypertension Division Chief

Dubai Hospital – DHA

21st March, 2019

Outline

• The Acute kidney injury (AKI)

• The Chronic Kidney Diseases (CKD)

• The Renal Replacement Therapies (RRT)

Case

• 4 yr male admitted with gram negative septic

shock. He is oliguric, 20% fluid overload, K of

6.8 meq/dl, Urea of 85 mg/dl, pH of 7.18.

Intubated on 85% FIO2, Peep of 10. BP is

80/40 on 0.6 mic/kg/min of norepinephrine

• He has AKI and needs RRT; How?

Pediatric AKI: Definition

Past: So many definitions…. Risk Injury Failure End-Stage Kidney Disease (RIFLE) Pediatric RIFLE (pRIFLE) Acute Kidney Injury Network definition

Crit Care. 2005; 9(5): 523–527

Vaidya et al. Annu Rev Pharmacol Toxicol. 2008 ; 48: 463–493. doi:10.1146

Vaidya et al. Annu Rev Pharmacol Toxicol. 2008 ; 48: 463–493. doi:10.1146

Pediatric AKI: Incidence in PICU

Population & Definition-dependent

0

5

10

15

20

25

30

35

40

45

50

No AKI R I F

58%

16% 17%

9%

0%

10%

20%

30%

40%

50%

60%

70%

No AKI Stage 1 Stage 2 Stage 3

Anesth Analg 2009;109:45–52

(Aprotinin study) Al-Kandari et al, ASN, 2008 Kid Int 2007; 71: 1028-35

82% AKI 21% AKI 42% AKI

Most Critically ill children

Vasopressors/Ventilated

Urinary catheter

pRIFLE

N=395

Cardiac Surgery

All PICU stay>48hrs

pRIFLE

0

10

20

30

40

50

60

70

80

90

No AKI R I F

Pediatric AKI:

Changing Epidemiology

Pediatric ARF Causes

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20

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40

50

60

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Sep

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Stickle SH et al: Am J Kid Dis 45:96-101, 2005

Previously: Primary renal diseases

Clinical Issues in AKI

• Oliguria:

– Volume overload and hypertension

– Inability to provide nutrition, therapy

• Diminished renal clearance:

– Electrolyte imbalance

– Acidosis

– Uremia

Conservative Management of AKI:

Traditional Methods

• Limit fluid intake

– Can reduce volume overload problems

– Can’t address issues of nutrition

• Limit input of retained substances

– Can reduce risks for hyperkalemia

– Can’t address imbalances from metabolism

• Adjustment of drug dosages in AKI

• Try not to mess up; wait and Hope

Do Diuretics Help in AKI?

1. Majority of

ICU patients

get diuretics

2. But no

improvement

in clinical

outcomes

Bagshaw CCM 2008 36(4)

8 non-randomized studies

6 randomized studies

Effect of Low-Dose Dopamine on Mortality

Friedrich JO, Adhikari N, Herridge MS et al. Ann Intern Med 2005; 142: 510–524

Low-dose dopamine increases urine output but

does not prevent renal dysfunction, the need for

RRT or death

Case

• Antenatal US: A male child with hypo-dysplastic kidneys and normal amniotic fluid

• Post-natal: Bilateral grade 4 VUR

• RFT: Creatinine continued to increase in first few months (4.5mg/dl at 6 months), UO normal-high

• PD started at 6 months, supplemental feeding + CKD - Meds; GH started at 1 year due to poor growth

• Transplant from Mom at 1.5 yrs. of age

• Currently: 6.5 years old, growing and thriving well, creatinine 0.6 mg/dl

Transplant

CKD: Impact on All Organs

• Bones can break, muscles can atrophy, glands can loaf, even the brain can go to sleep, and not endanger our survival; but should the kidneys fail in their task neither bone, muscle, gland nor brain could carry on.

From Dr. Homer. W. Smith: Fish to

Philosopher

Definition of CKD

• Kidney damage: Pathologic abnormalities or

markers of damage (abnormalities in blood

or urine tests or imaging studies)

or

• GFR <60 ml/min/1.73m2

Persistent for 3 months with implications for health

Renal Pathology in Progressive CKD

Regardless of the cause,

kidney in CKD shows:

Glomerulosclerosis

Vascular sclerosis

Tubulo-interstitial

fibrosis

Olson, Lab Invest 59:564-578, 1988

CKD: Incidence & Prevalence

• A serious public health problem, poor outcomes and high cost

• Increasing incidence with poor and ethnic minority disproportionately affected

• Rising incidence of obesity and type II DM in youth

• Prevalence of CKD: 18.5-58.3 per million children

Age, gender and racial differences:

Prevalence increases with age

Obstructive uropathies more common in males

CKD and ESRD: Higher in blacks

Stages of CKD

KDOQI KDIGO

Stage Description GFR (ml/min/1.73m2)

1 Kidney damage with

normal or ↑ GFR

≥90

2 Kidney damage with

mild ↓ GFR

60-89

3a

3b

Mild-Moderate ↓ GFR

Moderate-severe ↓ GFR

45-59*

30-44

4 Severe ↓ GFR 15-29*

5 Kidney failure <15*

Stage Description GFR (ml/min/1.73m2)

1 Kidney damage

with normal or ↑ GFR

≥90

2 Kidney damage

with mild ↓ GFR

60-89

3 Moderate ↓ GFR 30-59*

4 Severe ↓ GFR 15-29*

5 Kidney failure <15*

* Complications of CKD surface

All Transplant patients have CKD regardless of GFR

Causes of Pediatric ESRD: 2012-2016

CAUSE Incidence

(Percentage)

CAKUT/Cystic 40%

Glomerular Disease (e.g. FSGS) 20.1%

Secondary Glomerular Disease/Vasculitis 10.3%

Interstitial nephritis/pyelonephritis

(chronic)

5.2%

Hypertensive/large vessel disease 5%

Neoplasms/Tumors 2%

Diabetes Mellitus 2%

Complications of transplant 1.1%

Miscellaneous (e.g. SCD, HIVAN) 6.3%

Unknown 9.7%

Missing data 3.9%

Source: USRDS (usrds.org)-2018

eGFR in Children

Old Schwartz:

K x Length in cm/S. Creat (mg/dl)

0.45 in children <2 years

0.55 in female children 2-18 and pre-pubertal boys

0.7 in pubertal boys

New Schwartz:

K= 0.413 x Length in cm/S. Creat,

Creatinine measured by enzymatic method standardized to IDMS

Evaluation of CKD

• Diagnosis: R/O CKD in a child with poor growth, anemia, excessive thirst, polyuria, nocturnal enuresis, HT

• Assess severity: eGFR

• Complications: of CKD

• Comorbidities: CVD, growth and nutrition, sexual, neurocognitive and psychosocial development

• Risks: for progression of CKD and CVD

Signs of CKD

• Proteinuria-early

• Hypertension-early

• Increasing serum creatinine (decreasing GFR)-late

• Poor height growth-late

• Fatigue-very late

• Anorexia-very late

• Nausea/vomiting-very late

Risk Factors for Progression

Well Known

• Ongoing disease

(GN, Obstruction)*

• AKI *

• Albuminuria *

• Hypertension *

• Diabetes, insulin resistance *

• Nephrotoxic agents *

• Contrast *

• Puberty

Less well studied

• Anemia *

• Chronic inflammation

• Genetics

• Metabolic acidosis *

• Obesity *

• Hyperuricemia *

• Access to health care*?

• Lower SES

Chronic Disease Model for CKD

Renal Replacement Therapy

Indications

• Volume overload

• Metabolic imbalance

• Toxins (endogenous or

exogenous)

• Inability to provide

needed daily fluids due

to insufficient urinary

excretion

Goals

• Restore fluid, electrolyte

and metabolic balance

• Remove endogenous or

exogenous toxins as

rapidly as possible

• Permit needed therapy

and nutrition

• Limit complications

RRT Options AKI/CKD

• Hemodialysis, Peritoneal Dialysis, & CRRT

– Each has advantages & disadvantages

• Modality Choice guided by

1) Patient Characteristics

• Disease/Symptoms

• Hemodynamic stability

2) Goals of therapy

• Fluid removal, electrolyte correction, or both

3) Availability, expertise and cost

Walters et. al. Pediatr Nephrol 2008

Peritoneal Dialysis (PD)

• Continuous

• Low cost, easy application

• Low ultrafiltration

• Good CV tolerance

• Preferred in infants, especially

with congenital heart disease

• No extracorporeal circuit

• No anticoagulation

• Intermittent

• Blood perfuses

extracorporeal circuit

• High efficiency system

• Poor CV tolerance

• High level of complexity

• Vascular access/heparin

• Quick depuration of small

molecules and water

HemoDialysis (HD)

Continuous Renal Replacement

Therapy (CRRT)

• Continuous • Technically similar to HD • SLOW: depuration of small

molecules and water • Good CV tolerance

• High level of complexity

• Vascular access/heparin

RRT Options

Liao, Z et al. Artificial Organs 2003; 27: 802-807

Trends in Pediatric RRT

0%

10%

20%

30%

40%

50%

60%

1995 1999 2003

CRRT

PD

HD

Warady et al, Pediatr Neph 2000, 15:11-3

CRRT Increasing

Renal Replacement Therapy

USRDS 2018 Annual Data Report

Conclusions

Born: February 8, 1968

Died: May 28, 2010

Height: 4' 8" (1.42 m)

Contact information:

Loai Eid, MD, MSHS, FAAP, FASPN

Consultant Pediatric Nephrologist

Dubai Hospital - DHA

Mediclinic City, Al Zahra PVT & Saudi German Hospitals

Email: LaEid@dha.gov.ae

Loaieid@hotmail.com

Mobile: 0562704271