Prof. Dr. dr.Syarifuddin Rauf, SpAKBagian Ilmu Kesehatan Anak FK - UNHASRS Dr. Wahidin Sudirohusodo MakassarPost : Head Division of Department of Child HealthMedical Faculty, Hasanuddin University

Lecturer : - Pediatric Nephrology - Bioethics - Phylosophy

Pediatric Nephrology

Tabel. Sebaran penyakit ginjal anak yang dirawat inap di BIKA FK UNHAS RS Wahidin Sudirohusodo (2000 2004)

Jenis penyakit ginjalJumlah%Sindrom Nefrotik9039,0Glomerulonefritis akut7130,7Infeksi saluran kemih3213,9Gagal ginjal akut41,7Gagl ginjal kronik20,9Tumor ginjal208,7Kelainan kongenital sal. Kemih20,9Batu saluran kemih41,7Nefritis Schoenlein Henoch41,7Nefritis Lupus10,4Proteinuria persistent10,4Jumlah231100

Nephrotic Syndrome in Children Syarifuddin Rauf, Bagian Ilmu Kesehatan Anak RSU Wahidin Sudirohusodo,Fakultas Kedokteran UNHAS

1. Generalized oedema2. Heavy proteinuria(>50mg/kgbb)3. Hypoproteinemia(250mg/dl) (Hypercholestrolemia)NEPHROTIC SYNDROME

2INCIDENCEWilawirya (1992): 6 cases/100.000 population < 14 yr old/yrSex ratio : : : = 1,5 2 : 1Children:Adult = 15 : 1Age incidence : - Highest Inc. = 2-5 years - Less common : > 5 yearsDepartment of Child Health, Hasanuddin University / General Hospital Wahidin Sudirohusodo : 1-2 cases/month

3ETIOLOGYUnknown (idiopatik=primer)Acquired(sekunder): Diabetic MellitusGenetic factors : - Congenital NS (mutation on chromosom 19) - HLA antigens : HLA-DR7Predisposition: Allergy

4CLASSIFICATION Primary Glomerular diseasesMinimal Change NS (MCNS) 70-80%Focal Segmental Glomerulosclerosis (FSGS)Mesangiocapillary GlomerulonephritisMembranous NephropathySecondary diseases Henoch-Schoenlein PurpuraSystemic Lupus Erythematosus

5PATOMECHANISMSoluble antigen- antibody complexElectrochemic theory

8CLINICAL MANIFESTATIONSCongenital NS (Finlandia type)Placenta enlargementMassif oedemaGenetic mutation on chromosome 19Steroid sensitive NSResponsif to cortikosteroidMinimal change NS (MCNS) : 70-80%Steroid resistantNo/minimal response to cortikosteroidFocal glomerulosclerosis (FSGS)

9SYMPTOMS & SIGNSOedema :Pitting oedemaGeneralized : starting in periorbital regions face abdomen (ascites) extremities Pleural effusionsMassive anasarca scrotal or vulval oedemaNo hypertension or hematuriaNormal renal function

8MANAGEMENTHypoalbuminaemia (< 2 gr%)Salt-poor human albumin (plasbumin) 1 gr/kgBWFebrile / feels unwell / abdominal pain :AntibioticsDiuretic : Indications : severe oedema that causes dyspnoeSpecific treatment : corticosteroidProtocol : International Study of Kidney Disease in Children (ISKDC)

9PROTOCOL THERAPY OF NSCD = 4 weeksAD/ID = 4 weeksTap. off1- 2 thn123 4 5 6 7 8remissionremissionISKDC: 1. ISKDC

9PROTOCOL THERAPY OF NSCD = 6 weeksAD/ID = 6 weeksTap. off1 year1 2 3 45 67 8 9 10 11 12remissionremissionISKDC: 2. Arbeitsgemeinschaft fur Paediatrische Nephrologie (APN)

10PROTOCOL THERAPY OF RELAPS NSCDAD/IDTap. off1 year123 4remissionremissionCD until remission( 1 - 4 minggu )

Any Questions?

KESIMPULANSN pada anak bersifat idiopatik dan umumnya sensitif kortikosteroid. Pengobatan SN pada anak sebaiknya dimulai dengan prednison/ prednisolon yang setelah mencapai remisi, prednison / prednisolon dilanjutkan sampai mencapai dosis threshold selama 6 12 bulan.Bila terjadi relaps, apakah itu bersifat resistent atau dependen steroid maka dapat diberikan obat-obat immunosupresif lain, yang diberikan secara bersama-sama dengan steroid atau sebagai single tratment.Selain pemberian obat maka pada penatalaksanaan SN harus diperhatikan terapi penunjang..

Sindrom nefrotik relaps frekuen atau dependen steroidPrednison FD RemisiDiturunkan sampai dosis treshoid 0,1-0,5 mg/kgBB AD6-12 bulanPrednison AD + CPARelaps padaPrednison > 0,5 mg/kgBB ADLevamisol 2,5 mg/kgBB AD(4-12 bulan)Relaps pada prednison > 1 mg/kgBB ADatauEfek samping steroid meningkatCPA 2-3 mg/kgBB8-12 mingguRelaps prednison standarRelaps pada prednison > 0,5 mg/kgBB ADSiklosporin 5 mg/kgBB/hariselama 1 tahunGambar. Diagram pengobatan sindrom nefrotik relaps frekuen atau dependen steroid

MCNS(100%)Initial responder (93%)Initial nonresponder (7%)R/ 8 mgg I6 bln (sesudah R/ 8 mgg)Non relapser (36%)Infrequent relapser (18%)Frequent relapser (39%)Late responder (5%)Late non-responder (2%)Subsequent nonresponder (5%)Minimal Change NS(MCNS) after 8 weeks treatment of corticosteroid

GLOMERULONEFRITIS AKUT PASCA STREPTOKOKKUS (GNAPS)

Proliferasi dan inflamasi glomeruli Sekunder oleh mekanisme imunologik Antigen: bakteri, virus, parasit & zat lain.

1. Angka kejadian Lebih sering umur 6-7 thn, jarang < 3 thn Laki laki > perempuan (2:1) 10- 12 % kasus infeksi strept. hemolitikus grup A Kaplan: 50% kasus asimtomatik pd epidemi GNAPS didahului ISPA atau piodermi

2. Etiologi Streptokokus hemolitikus grup A (tipe M) NEFRITOGENIK Faringitis (serotipe tersering 12, lalu 1,3,4,6,25) Piodermi (serotipe tersering 49, lalu 2,53,55, 56,57,58,60

Periode latent: 1 3 mingguEdema HematuriHipertensi OligouriaGejala-gejala lain: lelah, malaise, letargi & anoreksia g. Kelainan laboratoriumMANIFESTASI KLINIK

URIN:Hematuri, warna kemerah-merahan atau seperti air dagingProteinuri : kualitatif dan kuantitatif> 6 bulan proteinuri persisten biopsi ginjal

DARAH:Titer ASTO meningkatMenurunnya kadar C3LED meninggiHipoproteinemi ringanPemeriksaan bakteriologik

Bila memenuhi 4 gejala berikut Hematuri makroskopik atau mikroskopik Edema Hipertensi ASTO meningkat C3 menurun Diagnosis GNAPS

SINDROM NEFROTIK (SN)

1. Edema Masif2. Proteinuri Masif3. Hipoproteinemi (< 2,5 g/dl)4. Hiperkolesterolemi (>250 mg/dl)

ANGKA KEJADIANAnak > dewasaAnak: 1 3 tahun > 5 tahunWila Wirya (1992): 6 kasus/100.000 penduduk < 14 thn/thnJumlah kasus di Indonesia (210 juta pend.) : 5040 SN

ETIOLOGITidak diketahui: SN idiopatikGenetik : SN kongenital HLA-B12, HLA B8Pencetus: Infeksi virus/bakteri Alergi

PATOMEKANISMESoluble antigen- antibody complexTeori elektrokemik

KOMPLIKASI YANG TERJADI PADA GNAPS DAN SN:

1.HIPERTENSI ENSEFALOPATI2. EDEMA PARU3. SYOK HIPOALUMINEMI4. GAGAL GINJAL

URINARY TRACT INFECTION(UTI)

Infection from renal parenchyme orificium urethrae externaSignificant bacteriuriaWith or without symptoms DEFINITION

2Pathogenic bacteriaColony count : > 100.000/ml urine> 1x lab. examinationsSignificant bacteriuria

TREATMENTConservative Treatment:The aims of this treatment:Preparing the child & family for the treatment of CRFSlowly progression to End Stage RF

3Relapsing UTI :Recurrent UTISame microorganismReinfection UTI :Recurrent UTIDifferent microrganism

2. Replacement therapy: The aims is to replace the function of the unfunction kidney by:Dialysis:Peritoneal dialysis (PD)HemodialysisTransplantation

ETIOLOGYBacteria :E. ColiKlebsiellaProteusPseudomonasOther microorganisms :ProtozoaVirus

CLASSIFICATION Clinically : 1. Symptomatic UTI 2. Asymptomatic UTIComplication :Simple UTI Complication UTILocalization : 1. Upper UTI 2. Lower UTI

PATHOGENESISHematogenicPercontinuitatumLymphogenic

Clinically :Upper UTI (Pyelonephritis) :Fever, back/flank pain & with or without lower UTI symptomsLower UTI (Cystitis) :Suprapubic punction, dysuria,frequent voiding etc.DIAGNOSIS

PATHOGENESISNeonatesBaby & Child(>1 month)Hematogen(Septicemia)Percontinuitatum(Ascending)Bacteria enter to Urinary tractSymptomatic UTI Asymptomatic UTIColonization on GITCertain focus : Periurethra/Perineum: Subpreputium?

LAB. EXAMINATIONSURINE : Urinalysis :Leukocyte > 5-10/HPFErythrocyte : +/-Urine culture :Mid : stream urine : C.C. : > 100.000/ml urineCatheterization :C.C. : > 10.000/ml urineSuprapubic punction :C.C. : > 1000/ml urine

BLOOD :LeucocytosisIncreased BSR (> 30 mm/hour)Increased CRP (> 30 ug/ml)

Eradicate acute infectionDetection, prevention, & treatmentrecurrent infectionDetection & surgical correctionabnormality of anatomical structureMANAGEMENT

KIDNEY :AGENESIS : BILATERAL RENAL AGENESIS = Potters SyndromeOligohydramnionPulmonary hypoplasiaLow-set earsRENAL HYPOPLASIA : The kidney is small Normal nephron

Horseshoe kidney : Fusion of the renal parenchymaJoined at the lower polePolycystic kidney :Infantile Polycystic Kidney (IPCK)Adults Polycystic Kidney (APCK)

BLADDER (VESICA URINARIA)AgnesiaBladder neck obstructionAgnesia / atresia urethraCongenital posterior urethral valvesURETHRA

URETERDuplication of ureterUreteroceleEctopic ureter

VESICO URETERAL REFLUXReflux of urine from the bladder into ureterDamage the upper urinary tract by bacterialInfectionCauses : Congenital anomalous developmentof the ureterovesical junctionBladder outlet obstruction

I P C KAutosomal Recessive Polycystic KidneyEnlargement of distal tubulus & colligents ductusGlomerulus & proximal tubulus normalLiver enlargement

Sudden loss or decreased of kidneys functionImbalance of water & electrolyte bloodIncreased of waste products (Ureum & Creatinin)

A. Prerenal: Decrased blood flowDiarrhea dehydrationHemorrhageBurnsSeptic shockETIOLOGY:

B. Renal: Acute Tubular NecrosisAcute Nephritic SyndromeNephrotic syndromeAcute Pyelonephritis

C. Postrenal: Urinary tract obstructionTumorsKidneystonesNephrocalcinosis

1. Prerenal:Perinatal hemorrhage (birth trauma, placenta abruption)Neonatal hemorrhage (severe intraventricular hemorrhage, adrenal hemorrhage)Perinatal asphyxiaHyaline membrane diseaseEtiology of ARF in Newborn:

2. Renal :Acute Tubular Necrosis (perinatal asphyxia)Maternal-fetal transfer:AntibodiesInfections: syphilis, Cytomegalovirus3. Postrenal : Congenital malformations of urinary collecting system

CLINICAL MANIFESTATIONS: Decreased urine volume (Oligouria Anuria)Generalized swellingChanges in mental status: UnconsciousDelirium/confusionComaSeizuresNausea, vomitingAnemiaKusmaul respiration

DIAGNOSIS Clinical Manifestations Lab. Examination:Serum Ureum increasedSerum Creatinin increasedCreatinin Clearance Serrum Potasium

TREATMENTThe goal of the treatment is to identify & treat reversible causes like prerenal causes (diarrhea dehydration) & post renal causes (e.g. obstructive uropathy by surgeon procedure)Medical drugs:Antibiotics: To prevent infectionDiuretics: to treat oligouria or anuriaDiazepam: To handle convulsion

3. Emergency condition:Hyperkalemia:Ca GlukonasPotassium exchange resin (Kayexalate) Oral/rectalMetabolic acidosis: Bicarbonate Natricus

Renal function progresses to decrease slowlyImbalance of water & electrolyte Increased of waste products (Blood ureum & creatinin)

< 5 years old: Hypoplasia / Dysplasia kidneyCongenital structure of urinary tractVesicoureteral refluxCongenital Nephrotic SyndromeETIOLOGY:

5 15 years old :Hereditary diseases: Alports syndrome, sistinuriPrimary glomerulonephritis: Nephritic SyndromeSecondary glomerulonephritis : SLE,SHS

Complication of SLEDamage to glomerulusProgressive loss of kidney function

GENERAL SYMPTOMSFeverMalar rash: A rash shaped like butterfly Usually found on the bridge of the nose & cheeksInflammation of the joints (arthritis)AnorexiaWeight lossAnemia

CLINICAL MANIFESTATIONS: RENAL SYMTOMPSPROTEINURIA: (+)(++) (30-100 mg/dl)Haematuria (+)/(-)ACUTE NEPHRITIC SYNDROMENEPHROTIC SYNDROME

DIAGNOSIS Clinical Manifestations Lab. Examination:Blood: Anti Nuclear Antibody (+)LE cell (+)Ds-DNA (+)C3 & C4

CLASIFICATION HISTOPATHOLOGICNormal histopathologic featureMesangial GlomerulonephritisFocal Segmental Proliferative GlomerulonephritisDiffuse Proliferative GlomerulonephritisMembranous Glomerulonephritis

TREATMENT Class I & II : Symptomatic treatment No specific treatment Class III,IV&V: Symptomatic treatment Specific treatmentCorticosteroidImmunosuppressive

VASCULITIS VASCULUS : PEMBULUH DARAHITIS : RADANGVASCULITIS : PERADANGAN PEMB,DARAH(AORTA SAMPAI KAPILER)

CONTOH : - PENYAKIT KAWASAKI - POLYARTERITIS NODOSA - SCHOENLEIN HENOCH SYNDROME - SYSTEMIC LUPUS ERYTHEMATOSUS

PENYEBAB : PROSES IMUNOLOGIK

SHS : Systemic disease Vasculitis on : Skin purpuraJoint arthritisDigestive tract abdominal painKidney glomerulonephritis

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) Autoimune disorderDamage to: Joints Heart Lungs Blood vessels Kidneys Skin

Age incidence :All ages75% of cases : 2-11 years Sex incidence : : = 2 : 1 50% of cases : preceded by upper respiratory infection group A streptococciINCIDENCE

PURPURA : Erythematous macular palpable purpuraEcchymoticAssociated with subcutaneous edema (extremities, scalp, periorbital region, hands, feet, scrotal area)Lower legs, ankles, dorsal foot ( symmetric)CLINICAL MANIFESTATIONS

2. Gastrointestinal Symptoms: Abdominal pain : 35-85% of casesGastrointestinal bleeding: melena, hematemesis, bloody stoolInvagination, intestinal perforation

3. Joint Symptoms: ArthritisArthralgiaAnkles & knees: most commonly affectedThe three signs: Classic triad of SHS

INCITING FACTOR (URIStreptococcus)IgA complexes (IgA1 & IgA2)Deposite in glom. basement membrane (gbm)Activate complementImmune complexes in gbm (IgA,IgG+C3)Renal symptomsPATHOPHYSIOLOGY

SYSYSTEMIC LUPUS ERYTHEMATOSUS

UnknownGenetic factor :HLA Antigen (HLA-DR2, HLA-DR3)High incidence in monozygotic twinHigh incidence in familyETIOLOGY :

3. Nongenetic factor:Longterm treatment of certain drugs (>6 months) hydralazineSex hormone: estrogen SLE (>)Viral infection

PATHOGENESISAutoimune processAntinuclear Antibody (ANA) + Ds-DNA (Antigen)Soluble Ag-Ab ComplexMBGDeposition of: ANA + Ds-DNA + C3Renal symptoms

URETERDuplication of ureterUreteroceleEctopic ureter

Haematuria associated with proteinuriaAcute Nephritic SyndromeNephrotic SyndromeRenal FailureRENAL INVOLVEMENT (SHS NEPHRITIS)

1. Self Limiting Disease2. Supportive & symptomatic Treatment:Fluid intakeAntihypertensive Hypertensive patientDiuretic OligouriaAntibiotic InfectionAnalgesics ArthralgiaMANAGEMENT

3. Specific treatment:Corticosteroid (Prednison 1-2 mg/kgBW)Severe Abdominal painGI bleedingRenal treatmentR/ Acute Nephritic syndrome Nephrotic Syndrome Renal Failure

KIDNEY :AGENESIS : BILATERAL RENAL AGENESIS = Potters SyndromeOligohydramnionPulmonary hypoplasiaLow-set earsRENAL HYPOPLASIA : The kidney is small Normal nephron

I P C KAutosomal Recessive Polycystic KidneyEnlargement of distal tubulus & colligents ductusGlomerulus & proximal tubulus normalLiver enlargement

BLADDER (VESICA URINARIA)AgnesiaBladder neck obstructionAgnesia / atresia urethraCongenital posterior urethral valvesURETHRA

BLADDER (VESICA URINARIA)AgnesiaBladder neck obstructionAgnesia / atresia urethraCongenital posterior urethral valvesURETHRA

VESICO URETERAL REFLUXReflux of urine from the bladder into ureterDamage the upper urinary tract by bacterialInfectionCauses : Congenital anomalous developmentof the ureterovesical junctionBladder outlet obstruction

*******************