AKI and CKD

Dr. Alao MA

Bowen University Teach Hosp Ogbomoso

AKI/ARF

1. What is a KDIGO definition of AKI?

• a. Increase in SCr by 26.5 umol/l AND anuria for 12 hours

• b. Increase in SCr at least 2x times baseline

• c. Increase in SCr by 26.5 umol/l within 48 hours OR urineoutput of 7 meq/L

2.What KDIGO AKI Stage is typically associated with poorpatient outcomes in children?

a. Any AKI(stage1,2or 3)

b. Stage 2 AKI or Stage 3 AKI

c. Stage 2 AKI only

d. Stage 3 AKI only

3. What is the differential diagnosis

• A 3-year old child is brought to the ED with 2-days historyof diarrhea and vomiting. The patient looks moderatelydehydrated. Investigations reveal: Na+ 146 mEq/l, K 4.8mEq/l, Creatinine 2.2 mg/dl, WBC 1500/mm3, normalplatelet count; urine specific gravity 1.007, no blood,protein 1+, Nitrite and leucocyte esterase negative. Nohydronephrosis is seen by an ultrasound examination of thekidneys.

Introduction

• Why AKI• Definition of AKI• Limitation of current definition • Causes/risk of AKI• Management • Prognosis

Ischuria renalis:William Heberden, 1802

Acute Bright’s disease: William Osler, 1909

Acute Renal Failure: Homer W. Smith, 1951

When to suspect?

Defining Acute Kidney Injury

• Historically: Lack a uniform definitionAnuria (urine output< 1ml/Kg/day) or oliguria

(urine output < 0.6mls/Kg/hr in neonates or

• EPIDEMIOLOGY:?????

• Incidence less than in adults

Note that up to 50% of ARF in children is non-oliguricN/B

• Anochie & Eke Paed Nephrol 2005 - hospital prevalence of 11.7 cases/year

• Olowu Ped Nephrol 2002 - ARF prevalence of 10 per million child population/yr

.

Defining AKI con’t

• Recently, the International Acute Dialysis Quality Initiative (ADQI) provided consensus definitions of ARF with the aim of standardizing the reporting of ARF and enhancing the understanding of both its treatment and prevention: the RIFLEclassification.

The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group4/13/2020 17

AKIN Staging Criteria for AKI

Mehta et al: Crit Care. 2007 Mar 1;11(2):R314/13/2020 18

A rapid decline in glomerular filtration rate GFRresulting in the disturbance of renal physiologicalfunctions including:

♦ Impairment of nitrogenous waste product excretion♦ Loss of water and electrolyte regulation♦ Loss of acid-base regulation

Definition:

When to suspect?

K

www.kdigo.org/home/guidelines/acute-kidney-injury

DIGO

OGIDK

KDIGO – AKI Definition

2.1.1: AKI is defined as any of the following:

§ Increase in SCr by ≥ 0.3 mg/dl (≥ 26.5 µmol/l) within 48hours; or

§ Increase in SCr to ≥ 1.5 times baseline, which is knownor presumed to have occurred within the prior 7 days; or

§ Urine volume

OD

KDIGO – AKI Definition

2.1.2: AKI is staged for severity according to the followingcriteria (Table 2)

IGK

KDIGO – AKI Definition

RIFLE

Increase in SCr ≥0.3 mg/Increase in SCr X 1.5 or dl or increase ≥150% to

GFR decrease > 25% 200% (1.5- to 2-fold) frombaseline within 48 h

KDIGO

Increase in SCr by ≥0.3 mg/dl

within 48 h or to ≥1.5 times baseline,known or presumed to have occurred

within the prior 7 d

AKIN

What is a KDIGO definition of AKI?

• a. Increase in SCr by 26.5 umol/l AND anuria for 12 hours

• b. Increase in SCr at least 2x times baseline

• c. Increase in SCr by 26.5 umol/l within 48 hours OR urineoutput of 7 meq/L

Risk

Injury

Failure

Loss

ESRD

UO 4weeks

End-stage renal

disease

(persistent failure >3 months)

eCCl decrease by25%

eCCl decrease by50%

eCCl decrease by

75% or eCCl <35ml/min/1.73

m2

(Akcan-Arikan, KI Int 2007)

Increase 0.3 mg/dl (27umol/L) during 48hours or increased

150%-200%

≥200%-300%

Increase ≥300%,serum creatinine

≥4mg/dL(≥354umol/L) or

dialysis orestimated GFR

CalculatedGFR =

½ the height of the patient

Serum creatinine

Measured

- Newborn - 0.3 to 1.0 mg/dL

- Infant - 0.2 to 0.5 mg/dL

- Child - 0.3 to 0.7 mg/dL

- Adolescent - 0.5 to 1.0 mg/dL

Schwartzformula

2016

The updated bedside Schwartz equation

k=0.413For all children

Serum creatinine concentrations may not changeuntil about 50% of kidney function has alreadybeen lost.Serum creatinine does not accurately reflect the GFRin a patient who is not in steady state.Creatinine is removed by dialysis.

This presents the need tofind new biomarkers to earlyidentify and manage AKI

○

○

Blood

Neutrophil gelatinousassociated lipocalin(NGAL)Cystatin C

○

○

○

UrineNeutrophil gelatinousassociated lipocalin(NGAL)Interleukin18 (IL-

18),

kidney injury

molecule-1 (KIM-1).

BIOMARKERS FOR AKI

○

○

○

○

Creatinine

Neutrophil gelatinousassociated lipocalin (NGAL)Interleukin18 (IL-18),kidney injury molecule-1(KIM-1).Cyctatin C

NGAL 0.9

Cystatin C 0.9

KIM-1 0.83

IL-18 0.75

Aetiology of AKI

• Nigerian Peculiarities

• Different aetiologic patternResults from mostly preventable causes and pattern not changed significantly over the years.

Secondary causes more prevalent than primary renal causes (Olowu & Adelusola 71% vs 29%).

Primary topped by Burkitt Lymphoma, AGN and Nephrotic syndrome at Ife while 20 was led by P. falciparum malaria and Septicaemia.

Anochie & Eke highlighted the importance of gastroenteritis and birth asphyxia.

Aetiology Anochie&Eke No./% 18yr Review-211 total

Olowu&AdelusolaNo./% A 9-yr Prospective study-123 total

Seriki No./% 1968-1970-23 total

Gastroenteritis 61 (28.9) 9 (7.3) 3 (13)

Septicaemia 32 (15.2) 25 (20.3) -

AGN 29 (13.7) 9 ( 7.3) 6 (26.1)

Nephrotic syndrome - 6 (4.9) -

P. Falciparum malaria 29 (13.7) 37 (23) 3 (13)

Birth asphyxia 27 (12.8) 37 (30) -

Congenital malformations

10 (4.7) 5 (%) PUV) -

HUS 7 (3.3) 2 (1.6) 1(4.3)

Malignancies 6 (2.8) 17 (13.8)Burkitt

Intravascular haemolysis

- 6 (4.9) -

HIV related 3 (1.4) -

Others (4.2) (4.9) 10(43.5)

Classification of AKI

Acute Kidney Injury

Pre-renal Intrinsic Post-renal

Glomerular Interstitial VascularTubular

4/13/2020

Pre‐renal

50-70%

Renal

20‐30%

Post‐renal

1‐10%

Leveling

PRE‐RENAL

Hypovolaemia

- haemorrhage -GIT losses

-hypoproteinaemia -burns

-DKA -renal & adrenal loss +

salt wasting

Hypotension

-septic shock -anti- hypertensives

-HF -pericardial tamponade

-DIC -hypothermia

-haemorrhage

-aortic clamping

-RDS

RENAL

Glomerulonephritis

-Poststreptococcal

-Lupus erythematosus

-Membranoproliferative

-Idiopathic rapidly progressive

-Henoch-Schönlein purpura

Localized intravascular coagulation

-Renal vein thrombosis

-Cortical necrosis

-Hemolytic-uraemic syndrome

Hereditary nephritis

Acute tubular necrosis-Heavy metals -Chemicals -Shock -Haemoglobinuria, myoglobinuria-Ischaemia

Acute interstitial nephritis-Infections -Drugs

Tumors-Primary or secondary infiltrative tumours-Uric acid nephropathy

Congenital anomaly-Cystic diseases -Dysgenesis

Postrenal

Obstructive uropathy

-Ureteropelvic junction

-Ureterocele

-Urethral valves

-Vesicoureteral reflux

-Tumours

Acquired

-Stones

-Blood clot

Causes ARF in the Newborn

-Renal dysgenesis

-Obstructive uropathy

-Renovascular accidents

-Congenital heart disease

-Dehydration

-Hemorrhage

-Systemic inflammatory response syndrome

-Sepsis

-Necrotizing enterocolitis

-Anoxia

-Shock

-Renal vein thrombosis

At Risk for AKI

At greater risk than others in Paediatrics are: • Post-surgical patients especially cardiac

surgery • Patients with Sepsis

• Those with underlying chronic renal or cardiac disorders

• Newborns requiring intensive care

Pathogenesis: AKI a theoretical

example

• AKI due to a reduction of RBF• Maladaptive molecular responses• These responses lead to endothelial &

epithelial cell injury following the onset of reperfusion

• In some cases is thought to lead to distant organ dysfunction syndrome

• leading to fatality in such patients

Mark Okusa & Rasheed Balogun 20104/13/2020 43

4/13/2020 44

PathogenesisKinsey GR, Li L, Okusa MD

Nephron Exp Nephrol. 2008Inflammation in AKI

Complex

Initiating events may be

dissimilar (ischemia or toxins)

subsequent injury responses

are similar pathways.

Pathogenesis: AKI

Factors such as vasoconstriction,

leukostasis, vascular congestion, apoptosis,

and abnormalities in immune

modulators and growth factors have formed

the basis of rational therapeutic

interventions.

Many these targeted therapies have failed,

are inconclusive or have yet to be

performed

4/13/2020 45

CLINICAL FEATURES

Features of ARF

-Decreased urine output

-Oedema

Features of complications

-Cough

-Diff.in breathing

-Seizures

-Loss of consciousness

-Anaemia; bleeding, dilutional ,haemolytic

-Hypertension +/- HF

-Bleeding; Uraemia, stress ulcers

Features of precipitating diseases

Non‐ oliguric ARF

-Aminoglycoside toxicity

-Resolving acute tubular necrosis

-Partial/intermittent urethral obstruction

Investigation

• Urinalysis

• EU Cr Ca2+ Po4 Uric acid

• Investigate for the cause•• Investigate for complication

Biochemical

Na+ -Normal or ↓6mmol/lHCo3 -↓1.5mg/dl

Biochemical

Urea - >45mg/dl

Other causes of high BUN

-High protein diet

-Steroid use

-Antianabolic drugs e.g. TCN

-Dehydration

-Increased production as in;

Surgery, trauma, infections, burns, fever, blood in

bowels, inadequate caloric intake

Comparison of lab. Finding in AKI

Management: Prevention & Early

Recognition + Intervention• Goals:

– Prevent death– Preserve renal function– Prevent complications of AKI– Prevent need for chronic RRT– Minimize adverse effects

• Relies on implementation of:– Non-pharmacological strategies– Pharmacological intervention– Renal supportive/replacement therapies

4/13/2020 52

MANAGEMENT• FLUID:

-Fluid challenge, if passing urine, likely pre renal cause.

Replace fluid deficit and ensure adequate hydration

-No response to fluid challenge and diuretics, likely

intrinsic renal problem

Restrict fluid to 300-400ml/m² + output

ELECTROLYTE DERANGEMENT

Hyperkalemia

AGENT DOSE ONSET MECHANISM

10% Ca gluconate 0.5-ml/kg10mins

Immediate CardioprotectiveCouteracts effects of HyperK

8.4% NaHCO3 2ml/kg IV 20 minutes Drive K+ into cell

Salbutamol 10mg via Nebs 5 minutes Drive K+ into cell

20% glucose+Insulin

2-5ml/kg

0.2U/kg over 1-2hrs

30 minutes Drive K+ into cell

Ion exchangeResin(Kayesalate)

1g/kg in 30% sorbitol PR or in 70% sorbitol orally.

2 hrs oral30 minutes PR

Remove K+

Dialysis PD/HFHaemo

GradualRapid

Remove K+

•Hyponatremia :Usually due to fluid retention, mx is

fluid restriction

•Hypocalcemia: Usually asymptomatic, if

symptomatic, treat with calcium gluconate

•Hypertension: Usually due to salt and water

retention, therefore start with diuretics if child is not

anuric.

•Seizure: Identify and treat cause, symp mx with anti convulsant

•Nutrition: Adequate calories, at least 1400kcal/m2

•Infection: Treat because may worsen outcome if untreated

•Dialysis: Early Initiation and not when patient is moribund

- Peritoneal dialysis

- Haemodialysis

- Continuous veno-venous haemofiltration/

-Continuous arterio-venous haemo-filtration

INDICATIONS FOR DIALYSIS ?????

• Symptomatic uraemia-Encephalopathy

- Pericarditis

- Bleeding

- Pulm oedema

• Fluid overload

• To deliver calories

• Electrolyte imbalance not responding to conservative treatment

Renal Supportive Therapy (RST) Options in AKI

• Hemodialysis, Peritoneal Dialysis, CRRT

• Each has advantages & disadvantages

• Modality choice guided by• Patient Characteristics

Disease/SymptomsHemodynamic stability

• Goals of therapyFluid removal, electrolyte correction, or both

• Availability, expertise and cost

18/8/2018

15

What Goes Wrong in AKI?

Volume issues

• Volume overload

• Pulmonary edema• Tissue edema• Congestive heart failure

• Hypertension (+/-)

Metabolic issues

• Chemical imbalance••••

Hyperkalemia

Metabolic acidosis

Hyperphosphatemia

Hyponatremia

• “Uremic” symptoms

Case

• A 6 year old male (22.4 Kg, 118 cm, BSA 0.85 m2), with ahistory of relapsing rhabdomyosarcoma received a stemcell transplant 17 days ago, and then developed fever,hypotension and respiratory failure three days ago. He isreceiving invasive mechanical ventilation (RR-20, 30/10,60% O2) and is receiving a continuous infusion ofnorepinephrine at 0.12 micrograms/kg/minute. His PICUadmission weight was 24.6 kg, and he developed a positivefluid balance of 3.8 liters since admission.

• Should we start renal supporttherapy for this patient now?

• Did you notice that I didn’t evenmention his serum creatinine?

18/8/2018

18

FluidBalance

Time

Maintenance/Homeostasis

Removal/Recovery

RESUCI

TATI

ON

Percent Fluid Overload Calculation

% FO at CRRT initiation =[ Fluid In - Fluid OutICU Admit Weight ] * 100%

Fluid In = Total Input from ICU admit to CRRT initiationFluid Out = Total Output from ICU admit to CRRT initiation

Author Year N FO(Surv) FO(Non-Surv)

Goldstein 2001 22 16% 34%

Gillespie 2004 77%FO>10%withORdeath3.02

Foland 2004 113 8% 17%

Goldstein(ppCRRT)

2005 116 14% 25%

Hayes 2009 76 7% 22%

Author FOThreshold Outcome

Goldstein Fluidthresholdsnotassessed

Gillespie 10%ORdeath3.02>10%FO

Foland 10%increment 1.78ORdeathforeach10%FOincrease

Goldstein(ppCRRT)

20% 20%FO:40%survival

Hayes 20% ORdeath6.1>20%FO

18/8/2018

19

Fluid Accumulation at Pediatric CRRT Initiationand Mortality

Fluid Overload Thresholds at CRRT Initiationand Mortality

18/8/2018

21

Question #4• Which statement is true regarding the considerations for

CRRT?a. KDIGO Stage 3 AKI should always lead to initiation of

CRRT

b. The standard indications for RST initiation in childrenwith end stage kidney disease serve as the model foracute RST initiation

c. Prevention of fluid accumulation of greater than 20% ofICU admission weight has the potential to improveoutcomes

d. CRRT should not be provided to patients with severeunderlying illness as it is futile

Where We are Heading

Funded by P50 DK096418-06

PROGNOSIS

• Depends on aetiology

• Mortality 10-60%

What KDIGO AKI Stage is typically associated with poorpatient outcomes in children?

a. Any AKI(stage1,2or 3)

b. Stage 2 AKI or Stage 3 AKI

c. Stage 2 AKI only

d. Stage 3 AKI only

CHRONIC RENAL DISEASE/CRF

Definitions • CRD: a complex of clinical, chemical and metabolic

disturbances that result from chronic reduction in renal function of which the essential feature is a reduced GFR.

• Chronic renal insufficiency is defined as a reduction of GRF to between 25 and 50% of (N).

Almost invariably progresses to CRF in spite of correction and arrest of the 1º cause.

• Chronic renal failure (CRF) can also be defined as a reduction of GFR to below 25% of (N) that has been present for at least 3 months.

Definition of Chronic Kidney Disease

• Kidney damage for ≥3 months, as defined by structural or functional abnormalities of the kidney, with without decreased GFR, manifest by either:

-Pathological abnormalities; or

-Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging tests

-GFR < 6 0 ml/min/1.73m² for ≥ 3 months, with or without kidney damage

Stages of Chronic Kidney Disease: A Clinical Action Plan

Stage Description GFR(ml/min/1.73 m²)

Action

1 Kidney damage >90 Diagnosis and treatment with normal or ↓GFRTreatment of co-morbid condition. Slowing progression, CVD risk reduction

2 Kidney damageWith mild GFR

60 - 89 Estimating progression

3 Moderate GFR 30 - 59 Evaluating and treating complications

4 Severe GFR 15 - 29 Preparation for kidney replacement therapy

5 Kidney failure

AETIOLOGY• Chronic glomerulenephritis

• Chronic pyelonephritis

• Renal dysplasia

• Cystic diseases

• Urologic abnormalities- Obstructive uropathies- Reflux nephropathy- Urinary tract malformations

• Systemic - SLE, H.S.P.

• Vascular - HUS

• Tumours - Bilateral Wilms

AETIOLOGY

• Chronic glomerulonephritis 25.8%• Reflux nephropathy and

obstructive uropathy 24.2%

Hereditary/familial 15.6%

Dysplasia 13.5%

Multisystem dx 10.2%

N:B -Majority of cases in Nigeria are due to steroid resistant nephrotic syndrome. EdtaData

*******PATHOGENESIS

• Once critical level of deterioration reached

↓

Progression

Hyperfiltration

Phosphate retention

Proteinuria

CLINICAL FEATURES

• Antenatal detection of conditions that can cause CRF

• Failure to thrive

• Short stature

• History of recurrent UTI

• Enuresis

• RESP- Acidotic breathing

- Uraemic breath

- Pulmonary oedema

- Plural effusion

- ARI

• CVS

-Hypertension

-CCF

-Uraemic - pericarditis

-Arrhythmias

• HAEMATOLOGY

-Pallor-Bleeding

• GIT-Anorexia

-Vomiting

-GI bleeding

• CNS- Seizure- Uraemic encephalopathy

• MSS- Renal osteodystrophy

• SKIN- Pruritus- Uraemic frost

INVESTIGATIONS• Group I (To assess severity of CRF)

FBC

Biochemistry- U&E, cr,

• Calcium, P04, Alkaline phosphatase, Albumin• GFR• PTH• X-ray of hand and wrist to assess bone age and features of renal

osteodystrophy (Subperiosteal erosion best seen in the middle phalanges)

• CXR• ECG, Echo

• Group 2 (To find the underlying cause of CRF)• Renal USS, MCUG, DMSA• Urinalysis + m/c/s• Immunology C3, C4, ANF, DsDNA, ANCA• Renal biopsy• White cell cystine, oxalate excretion

Renal Function

• Technitium-99m DMSA (Dimercaptosuccinic acid) Scan for detecting renal parenchynal scarring

• DTPA (Diethylene triamine pentacetic acid) for assessing renal plasma flow.

• Technitium-labelled Mercaptoacetyltriglycine (MAG3)–reflects proximal tubular excretion of isotope

• DTPA & MAG3 in dynamic renography to rule out obstructive uropathy.

MANAGEMENT

• Pre-terminal• Objectives are:

-To make the child feel normal and be seen

to be normal by mates

-Slowing progression to ESRF

-Maintain normal growth

-Preserving normal family milieu

-Prepare family for mx of ESRF

MANAGEMENT (CONTD)

• Team-Nephrologist, Specialist Nurse, Dietician, Social Worker,

Psychologist/Psychiatrist, Teacher, Play specialist

• GROWTH: Majority usually growth failure prior to presentation

-Find out why child is not growing

-Use of recombinant GH 0.9 iu/week

• NUTRITION

-Ensure adequate calorie intake 100-120cal/kg

phosphate restriction

Protein normal

• FLUID AND ELECTROLYTE BALANCE

• METABOLIC ACIDOSIS: To ensure adequate growth and prevent demineralization of bone

-NaHCO3 at 2mmol/kg

• BONE (Renal osteodystrophy)-Use of phosphate binder Calcium carbonate

-1,25-dihydroxycholecalciferol 0.02microgram/kg/day, titrate with PTH

HYPERTENSION

• Diuretics• ACEI• Nephrectomy

ANAEMIA

• Ensure adequate iron and folate store

• Use of EPO 50iu/kg 3x/week

MERITS OF RECOMBINANT HUMAN ERYTHROPROTEIN THERAPY

Benefits Potential ComplicationsAvoids/Minimizes blood transfusion Iron deficiency

Reduced sensitization toHistocompatibility antigens

Most require iron therapyHypertension

Reduced exposure to infectious diseases

Seizures

Improved appetite Decreased dialyzer clearance

Enhanced physical fitness HYPERKALEMIA

Increased activity during day Clotting of vascular access

Improved sleep Pure red cell aplasia (in adults due to rHuEPO antibodies)

Improved well-being

• ESRD Mx

• RRT initiated when GFR

PROGNOSIS

• improved in the last 25 years in developed countries

• ESRF is still a death sentence for a Nigerian child.

We therefore have to concentrate on preventive

nephrology.

The predisposing factors like hypertension and

diabetes should be focused on.

The incidence of hypertension in our Nation is

about 12% while that of Diabetes is 2% and

fast increasing.

Renal Osteodystrophy

The definition of CKD-MBD is:

A systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:

• Abnormalities of calcium, phosphorus, PTH or vitamin D metabolism

• Abnormalities in bone turn over, mineralization, volume, linear growth or strength

• Vascular or other soft tissue calcification

Renal Osteodystrophy

Clnical features:

• Muscle weakness, bone pain, and fractures with minor trauma.

• In growing children, rachitic changes, varus and valgus deformities of the long bones, and slipped capital femoral epiphyses

• Laboratory studies may demonstrate a decreased serum calcium level, increased serum phosphorus level, increased alkaline phosphatase, and a normal PTH level.

Renal Osteodystrophy

Renal Osteodystrophy

Radiographs of the hands,

wrists, and knees show

subperiosteal resorption of

bone with widening of the

metaphyses.

The skeletal pathologic

finding in this condition is

osteitis fibrosa cystica.

• Thank You