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Curriculum Vitae

Nama: Partini Pudjiastuti Trihono Pendidikan: Dokter umum: FKUI 1979 Spesialis Anak: FKUI 1989 Master of Medicine (Paediatrics): University of Melbourne 1996 Pediatric Nephrology course: Royal Children Hospital Melbourne 1996 Spesialis Anak Konsultan: IDAI 1999 Doktor: FKUI 2007 Jabatan sekarang:
Ketua Program Studi IKA FKUI Ketua Divisi Nefrologi Departemen IKA FKUI Wakil Ketua Kolegium IKA Indonesia

CHRONIC KIDNEY DISEASE: DIANOSIS AND MANAGEMENT

Partini Pudjiastuti Trihono Department of Child Health Faculty of Medicine University of Indonesia

Batam, 8 June 2013

Definition of CKD
Structural or functional abnormalities of the kidneys for >3 months, as manifested by either: 1. Kidney damage, with or without decreased GFR, as defined by
pathologic abnormalities markers of kidney damage, including abnormalities in the composition of the blood or urine or abnormalities in imaging tests

2. GFR <60 ml/min/1.73 m2, with or without kidney damage


NKF-KDOQI CPG AJKD 2002: 39(2)

Classification of CKD
Stage 1 Kidney damage w/ normal GFR GFR >= 90 ml/min/1.73 m

Stage 2 Stage 3

Kidney damage w/ mild 60-89 GFR decrease mild Moderate GFR decrease 30-59 moderate

Stage 4
Stage 5

Severe GFR decrease


Kidney failure (ESRD)

15-29 severe
< 15 or on dialysis

NKF - K/DOQI (KIDNEY DISEASE OUTCOME QUALITY INITIATIVE) - Am J Kidney Dis 2002

PROGRESSION OF CHRONIC KIDNEY DISEASE


Systemic hypertension
Hyperfiltration

Reduced nephron mass

INTRAGLOMERULAR HYPERTENSION

Glomerular hypertrophy

Increased filtration pressure Tubulointerstitial hypoxia Podocyte injury

Proteinuria
Vasoactive signaling
Matrix deposition

Proinflamatory signaling

FIBROSIS

Causes of CKD
Glomerulonephritis

Primary: nephrotic syndrome, focal segmental glomerulosclerosis Secondary: SLE, Henoch-Schonlein


Alport syndrome, congenital nephrotic syndrome Bilateral renal dyslasia, hypoplasia, polycystic kidney disease Reflux nephropathy

Familial nephropathy

CAKUT (congenital anomalies in kidney and urinary tract)

Obstructive uropathy

PUJO, VUJO, calculi


Bilateral Wilms tumor Renal cortical necrosis

Miscelaneous

Risk Factors for CKD


VUR associated with recurrent UTI and renal scarring Obstructive uropathy Prior history of acute nephritis or nephrotic syndrome History of renal failure in perinatal period Family history of polycystic kidneys or genetic renal conditions Renal dysplasia or hypoplasia Low birth weight infants History of Henoch-Schonlein purpura Presence of diabetes, hypertension Systemic lupus erythematosus, vasculitis

DIAGNOSIS

Modes of presentation of CKD


Antenatal ultrasound scanning Abdominal mass Urinary tract infection Enuresis Failure to thrive Short stature Lethargy and pallor Hematuria Nephrotic syndrome Hypertension Congestive cardiac failure Seizures Failure to recover from acute renal failure Screening siblings of index cases

Simple assessment of GFR in children


Schwartz formula: GFR= body height (cm) x K Pcr (mg/dL)

K= K= K= K=

0.45 0.55 0.57 0.70

for for for for

babies < 1 year old boys and girls 1-13 year old girls > 13 year old boys > 13 year old

This equation gives the GFR in ml/min./1.73 m2 BSA The problem is, the Schwartz formula does not work so good in children with very high plasma creatinine levels.

Chronic renal failure


Main consequences
Mechanism Decreased excretion Example Uremic toxins Salt and water Phosphate Acid Potassium Erythropoietin Activation of vitamin D Clinical Manifestations Uremic syndrome Volume overload, hypertension Hyperparathyroidism Metabolic acidosis Hyperkalemia Anaemia Osteomalacia, Hyperparathyroidism

Decreased biosynthesis

Altered metabolism

Dyslipidaemia Glucose intolerance

Atherogenesis

Uremic Syndrome: manifestations


Cardiovascular
Hypertension Cardiomyopathy Arrhythmias Cardiac failure Arteriosclerosis Pericarditis

Coagulation System Respiratory System Endocrinology and metabolism


Bleeding Hypercoagulation

Pneumonitis, uremic lung Lung edema

Central Nervous System


Insomnia Fatigue/spasm Tremor asterixis, myoclonus Confusion, stupor, coma Encephalopathy EEG changes

Glucose intolerance Abnormal lipid metab. Abnormal amino acids metab, Malnutrition Hypoalbuminemia Muscle wasting Growth retardation Hypothermia

Uremic Syndrome: manifestations


Peripheral Nervous System
Polyneuropathy Paresis Autonomic neuropathy Hypotension

Skin

Hematology and Immunology


Anemia Susceptible to infection Granulocyte dysfunction Lymphocyte dysfunction Immunodeficiency Malignancy

Skin dry Pruritus Hyperpigmentation Bleeding Delayed wound healing

Gastrointestinal System
Anorexia Nausea, vomiting Hiccup Stomatitis Gastritis Parotitis Colitis Bleeding Fetor uremicum

Musculo-sceletal System

Osteodystrophy, osteomalacia Hyperparathyroidism Pain and fracture Carpal Tunnel syndrome Amiloidosis Myopathy Muscle weakness

Diagnosis and Assessment Severity


Investigations
Urinalysis Blood: complete blood peripheral, urea, creatinine, Ca, PO4, alkaline phosphatase, PTH, iron, ferritin, blood gas Radiology: CXR, bone age ECG Kidney ultrasound: renal size, anomalies, obstruction MSU, DMSA (not helpful if GFR <20-30 mL/min/1.73 m2) Renal biopsy (for glomerulonephritis)

PRINCIPAL MANAGEMENT
1. Early detection and prompt treatment kidney diseases 2. Slowing progression of CKD 3. Prevention and management of complications

Early treatment can make a difference


100 No Treatment

GFR (mL/min/1.732)

Current Treatment Early Treatment

10 0

Kidney Failure
4 7 9 11

Time (years)

dfschaffner@BeckmanCoulter.com

ASN

Clinical Practice Guidelines for the Detection, Evaluation and Management of CKD
Stage Description At increased risk Kidney damage with normal or GFR Kidney damage with mild GFR Moderate GFR Severe GFR Kidney Failure
1

GFR

Evaluation Test for CKD Diagnosis Comorbid conditions CVD and CVD risk factors Rate of progression Complications

Management Risk factor management Specific therapy, based on diagnosis Management of comorbid conditions Treatment of CVD and CVD risk factors

>90

60-89

Slowing rate of loss of kidney function 1

3 4 5

30-59 15-29 <15

Prevention and treatment of complications Preparation for kidney replacement therapy Referral to Nephrologist Kidney replacement therapy

Target blood pressure less than 130/80 mm Hg. Angiotension converting enzyme inhibitors (ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mg/g.

Slowing progression and treatment of complications


Fluid and salts intake Nutrition Proteinuria Hypertension Anemia Metabolic acidosis Infection Secondary hyperparathyroidism Ca and P metabolisms/bone and mineral disorder

Fluids and salt intake


Maintain hydration
Beware of polyuria Adequate hydration: attention to fluid intake and urine output

Correct electrolyte disturbances


Hyponatremia Hypo / hyperkalemia Hyperhosphatemia Hypo / hypercalcemia

Nutritional and dietary management


Adequate calorie intake for maintenance and catch-up growth Adequate protein intake for growth (RDA, higher biologic value protein) Low phosphate intake Salt / potassium restriction Vitamins and trace elements supplementation

Proteinuria
Screening:Test first morning urine sample
Protein >+1: do protein to creatinine ratio

Monitoring: protein to creatinine ratio on first morning urine sample


Spot urine for albumin/creatinine ratio (mg:mg)
Normal = <0.2 (0.5 if <2yr) Proteinuria= >0.2; Nephrotic range=> 2

Treatment:
ACEI: captopril, enalapril ARB : losartan both

ACEI +/- ARB


Beware of hypotension, deterioration of kidney function, hyperkalemia Decrease in GFR, usually within 4 weeks:
Decrease < 30%: acceptable Decrease 30%-50%: dose adjustment Decrease > 50%: drug withdrawal

Hypertension
Treatment should be aggressive Target: BP level < 90th centile for specific age, sex, and height Hypertension related to hypervolemia diuretics thiazide or furosemide Others anti-hypertensive agents:
ACEI +/- ARB Ca channel blocker: amlodipine, nifedipine Selective -blocker: atenolol Vasodilators: hydralazine

Etiology of anemia in CKD: MULTIFACTORIAL


Erythropoietin deficiency Erythropoiesis inhibitor Secondary hyperparathyroidism Blood loss Deficiency of hematinic agents (Fe,folic acid, B12) Shorter erythrocytes lifespan Primary renal diseases Cytokine inflammation Infection Aluminium toxicity

GFR < 60 mL/m/1.73 m2 Hb level

GUIDELINE NKF - K/DOQI


Am J Kidney Dis, 2002 (mod)

Hb < 11 g/dL
Complete peripheral blood Iron index Normal Treat with r-EPO No Iron deficiency No Refer to hematologist

Iron supplement Anemia corrected

Anemia persisted

TREATMENT ANEMIA WITH r-HuEPO


Indikasi : Hb < 10 g/dl atau Ht <30 % Target : Ht 33 - 36 % (NKF-K/DOQI) Ht > 30 % (PERNEFRI) Dosages: start with 50 unit/kg SC, twice a week

Pre-requisite:
1. 2. 3. 4.

Adequate iron storage: feritin serum >100 g/L transferin > 20% No infection/inflammation No hyperparathyroidisms Avoid iron overload

Packed Red Cell Transfusion


Indications 1. Acute bleeding 2. Hb< 7 g/dl but r-EPO is not available 3. Hb<8 g/dl with hemodynamic failure 4. Iron deficiency patients who will have r-EPO or inadequate responds to EPO Target Hb 7 - 9 g/dl

!!

Adverse effects of transfusion

Acid base status


Maintenance of acid base balance is important Metabolic acidosis associated with
Failure to thrive, muscle degradation, bone demineralization, hyperkalemia

Correction: Reducing protein intake ( S- containing amino acids) Reduce endogenous acid production Sodium bicarb. supplementation (dose adjusted to BGA)

Feedback Loops in 2nd Hyperparathyroidism


Decreased Vitamin D Receptors and Ca-Sensing Receptors

PTH

PTH

Ca++
Bone Disease Fractures Serum P Bone pain Marrow fibrosis Erythropoietin resistance

1,25D Calcitriol

Systemic Toxicity CVD Hypertension Inflammation Calcification Immunological

25D
Renal Failure
Ca = calcium; CVD = cardiovascular disease; P = phosphorus.
Courtesy of Kevin Martin, MB, BCh.

Ca and PO4 metabolism in CKD


Monitor Ca, PO4, alkaline phosphatase, PTH, Xray renal osteodystrophy view (knee or wrist) Restrict dietary phosphate Phosphate binder
CaCO3 50-100 mg/kg BW taking during meals Ca acetate Sevelamer

Vitamin D3 (1,25 diOH cholecalciferol) Calcium supplement (watch carefully for hypercalcemia)

Target ranges for blood biochemical parameters in children with CKD


Ca mg/dL Age 1-12 yrs CKD 2-3 CKD 4 9-10.2 9-10.2 4-6 4-6 <65 <65 35-70 70-110 100-450 100-450 P mg/dL Ca x P PTH pg/mL ALP mg/dL

CKD 5
Age > 12 yrs CKD 2-3 CKD 4 CKD 5

8.8-9.7

4-6

<65

200-300

100-450

8.8-10.2 8.8-10.2 8.8-9.7

2.5-4.5 2.5-4.5 3.5-5.5

<55 <55 <55

35-70 70-110 200-300

40-180 40-180 40-180

Vaccination of Patients with Chronic Renal Disease

Factors affecting renal disease progression


CKD Progression
Renal anemia, dyslipide mia Altered mineral homeostasis

Hypertension

Protein uria

Anemia of Renal Failure

dfschaffner@BeckmanCoulter.com

KDOQI RECOMMENDATION
Ca

Maintain in normal range


CKD stage 5: > 12 year 1-12 year

PO4
3.4-5.5 mg/dL 4 6 mg/dL

PTH
CKD stage 4: 70-110 pg/ml CKD stage 5: 200-300 pg/ml > 12 year : 55 mg2/dL2 < 12 year : 65 mg2/dL2

Ca x PO4

Growth
Possible factors contributing to growth retardation in CRF

Inadequate energy intake Inappropriate protein intake Disturbance of water and electrolyte balance Metabolic acidosis Renal osteodystrophy Hypertension Infection Anemia Hormonal abnormalities Corticosteroid therapy Psychosocial factors
Recombinant human growth hormone when optimal management fails

Vaccination of Patients with Chronic Renal Disease Recommended:


BCG Hepatitis B Varicella zoster Pneumococcus Influenza

Chronic Kidney Disease


Common condition Most etiology:
Glomerulonephritis Reflux nephropathy Obstructive uropathy
Infection Congenital UT anomalies

Significant morbidity Expensive Effective treatment can slow progression Teamwork: primary physicians, pediatricians, renal specialists

Stages in Progression of Chronic Kidney Disease and Therapeutic Strategies


Complications

Normal

Increased risk

Damage

GFR

Kidney failure

CKD death

Screening for CKD risk factors

CKD risk reduction; Screening for CKD

Diagnosis Estimate Replacement & treatment; progression; by dialysis Treat Treat & transplant comorbid complications; conditions; Prepare for Slow replacement progression

AJKD 2002: 39(2)

Chronic kidney disease Pathophysiology of 2nd hyperparathyroidism

Phosphate retention

FGF23

1,25(OH)2D3

PTH resistance of bone Hypocalcemia Acidosis

Hyperparathyroidism
Parathyroid Ca receptor expression Parathyroid 1,25(OH)2D3 receptor expression

Recommended target ranges for serum PTH and Ca-Po4 product


Target range
II

Chronic Kidney Disease Stage


III IV V

Serum PTH level


Ca-PO4 product level

35-70 pg/ml

35-70 pg/ml

70 -110 pg/ml

200-300 pg/ml

Age < 12 years < 65 mg2/dL2 Age > 12 years < 55 mg2/dL2

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