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AKI and CKD
Dr. Alao MA
Bowen University Teach Hosp Ogbomoso
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AKI/ARF
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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
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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
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3. What is the differential diagnosis
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• 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.
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Introduction
• Why AKI• Definition of AKI• Limitation of current definition • Causes/risk of AKI• Management • Prognosis
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Ischuria renalis:William Heberden, 1802
Acute Bright’s disease: William Osler, 1909
Acute Renal Failure: Homer W. Smith, 1951
When to suspect?
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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
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• 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
.
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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.
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The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group4/13/2020 17
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AKIN Staging Criteria for AKI
Mehta et al: Crit Care. 2007 Mar 1;11(2):R314/13/2020 18
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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?
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K
www.kdigo.org/home/guidelines/acute-kidney-injury
DIGO
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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
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OD
KDIGO – AKI Definition
2.1.2: AKI is staged for severity according to the followingcriteria (Table 2)
IGK
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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
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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
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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
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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
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2016
The updated bedside Schwartz equation
k=0.413For all children
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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.
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This presents the need tofind new biomarkers to earlyidentify and manage AKI
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○
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Blood
Neutrophil gelatinousassociated lipocalin(NGAL)Cystatin C
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UrineNeutrophil gelatinousassociated lipocalin(NGAL)Interleukin18 (IL-
18),
kidney injury
molecule-1 (KIM-1).
BIOMARKERS FOR AKI
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○
○
○
○
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
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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.
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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)
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Classification of AKI
Acute Kidney Injury
Pre-renal Intrinsic Post-renal
Glomerular Interstitial VascularTubular
4/13/2020
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Pre‐renal
50-70%
Renal
20‐30%
Post‐renal
1‐10%
Leveling
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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
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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
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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
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Postrenal
Obstructive uropathy
-Ureteropelvic junction
-Ureterocele
-Urethral valves
-Vesicoureteral reflux
-Tumours
Acquired
-Stones
-Blood clot
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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
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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
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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
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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.
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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
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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
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Non‐ oliguric ARF
-Aminoglycoside toxicity
-Resolving acute tubular necrosis
-Partial/intermittent urethral obstruction
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Investigation
• Urinalysis
• EU Cr Ca2+ Po4 Uric acid
• Investigate for the cause•• Investigate for complication
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Biochemical
Na+ -Normal or ↓6mmol/lHCo3 -↓1.5mg/dl
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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
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Comparison of lab. Finding in AKI
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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
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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
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ELECTROLYTE DERANGEMENT
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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+
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•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.
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•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
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INDICATIONS FOR DIALYSIS ?????
• Symptomatic uraemia-Encephalopathy
- Pericarditis
- Bleeding
- Pulm oedema
• Fluid overload
• To deliver calories
• Electrolyte imbalance not responding to conservative treatment
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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
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18/8/2018
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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?
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18/8/2018
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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
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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
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Fluid Accumulation at Pediatric CRRT Initiationand Mortality
Fluid Overload Thresholds at CRRT Initiationand Mortality
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18/8/2018
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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
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PROGNOSIS
• Depends on aetiology
• Mortality 10-60%
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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
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CHRONIC RENAL DISEASE/CRF
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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.
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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
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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
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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
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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
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*******PATHOGENESIS
• Once critical level of deterioration reached
↓
Progression
Hyperfiltration
Phosphate retention
Proteinuria
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CLINICAL FEATURES
• Antenatal detection of conditions that can cause CRF
• Failure to thrive
• Short stature
• History of recurrent UTI
• Enuresis
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• 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
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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
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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.
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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
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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
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• 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
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HYPERTENSION
• Diuretics• ACEI• Nephrectomy
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ANAEMIA
• Ensure adequate iron and folate store
• Use of EPO 50iu/kg 3x/week
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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
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• ESRD Mx
• RRT initiated when GFR
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PROGNOSIS
• improved in the last 25 years in developed countries
• ESRF is still a death sentence for a Nigerian child.
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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.
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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
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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.
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Renal Osteodystrophy
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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.
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• Thank You