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NEPHROTIC SYNDROME STEROID RESISTANT

BY : JEREMY THOMPSON GINTING (090100057) IRENE ARIFIN (090100232) SUPERVISOR : DR.SELVI NAFIANTI,Sp.A(K)

DEFENITION,EPIDEMIOLOGY,INCIDENCE
 Characterised by proteinuria (3.5g per 24 hours),

hypoalbuminemia (serum <30g/dL), oedema, hypercholesterolemia  Almost always idiopathic in childhood  Nephrotic syndrome (NS) reflects glomerular dysfunction causing proteinuria without compromising GFR  Occurs at all ages but is most prevalent in children between the ages 1.5-6 years  It affects more boys than girls, 2:1 ratio  Most studies put the incidence at 2-7 per 100,000 population

Definitions
 Remission – negative urinalysis on 1st morning

urine for 3 consecutive mornings  Relapse – 3+ proteinuria on 3 or more consecutive 1st morning urines  Frequently relapsing – 2 or more relapses within 6 months of diagnosis; or 4 or more relapses per year  Steroid resistant – no remission after 4 weeks of prednisolone 60mg/m2/day

ETIOLOGY PRIMARY NS  Minimal Change Disease (MCD)  Focal Segmental Glomerulosclerosis (FSGS)  Membranoproliferative Glomerulonephritis  (Membranous Nephropathy) .

PROGNOSTIC Multiple aetiologies .Idiopathic NS Spectrum: from MCD to FSGS 80-90 % MCD Non Infrequently Relapsing Relapsing Frequently Relapsing Steroid Dependent Steroid Resistant ~90 % Steroid Sensitive .

Secondary Causes             SLE Infection HIV Hepatitis B and C Malaria Syphilis Obesity – generally lower proteinuria and less edema Drug exposure NSAID Henoch Schonlein Purpura Malignancy (Rare in children) Diabetes is not a cause of NS in children due to long latency .

1)mechanism of glomerular injury 2)proteinuria  Circulating non-immune factors in MCD and FSGS  Circulating immune factors in disorders membranoproliferative GN. poststreptococcal GN and SLE nephritis  Mutations in podocyte or slit diaphragm in inherited form of congenital.Pathophysiology  Two important issues. infantile or glucocorticoid resistant nephrotic syndrome .

Presentation  First sign usually facial swelling –     periorbital oedema Increasing oedema over days to weeks Lethargy. weakness. poor appetite. abdominal pain May follow an apparent viral URTI Haematuria/hypertension unusual .

HIV.How to diagnose SNRS?       Diagnosis based on history and clinical findings Urine dipstick 24 hour urine collection U&E FBC +/. antinuclear antibodies . varicella serology  Renal US  Others –serum protein electrophoresis. serum complement.Hepatitis serology.

Renal biopsy  Rarely performed in Paediatric cases  Consider if.  Congenital Nephrotic Syndrome  > 8 years at onset  Steroid resistance  Frequent relapses  Significant nephritic manifestations .

A diet with no added salt will help to limit fluid overload.5mg/\dl) Captopril if hypertention is found . Furosemide 1-3mg/BW/day Spironolactone 2-4mg/BW/day Albumin (>/ 2.Treatment  Prednisolone 60mg/m2/day x 4 weeks. Supplemental dietary protein is of no proven value. and reduce alt day dose by 10mg/m2 every 3 days until 10mg/m2 alt days – then 5mg/m2 alt days for three doses then STOP Adequate protein energy (caloric) intake and adequate protein (1-2 g/kg/d). 40mg/m2       alternate days for 4 weeks then STOP For relapse – prednisolone 60mg/m2/day until remission. then 40mg/m2 alt doses for 3 doses.

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Frequently Relapsing or Steroid dependent NS     Cyclosporin A Tacrolimus Cyclophosphamide Mycophenolate mofetil .

relative immobility. symptoms – oliguria. nephrotoxcity from cyclosporin A or tacrolimus . steroid therapy  Hypovolemia – shift of fluid from intravascular space. loss of immunoglobulins.Complications  Infection – typically with Strep pneumoniae (pneumonia or peritonitis) (oedema &peritoneal fluid. anorexia. abd pain. postural hypotension  Drug toxicity – side effects of steroid treatment. increased haematocrit. immunosupression)  Thrombosis – loss of antithrombin III and proteins S&C in urine. increased procoagulant factors by liver.

Prognosis Minimal Change FSGS MPGN Often Relaps Over 90% Resolves with no permanen kidney damage Usually results in CKD (>50%) in 5-10 years 50% CKD within 510 years .

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no bloody urination. The patient had fever since 2 days ago. not so high in temperature and reduced by consumption of antipyretic drugs. then spread to the entire body. Patient was admitted to a local hospital and was given the drug Prednisone. but a foamy urination was found.5 kg BW/A: 23/19 x 100% = 121% H/A: 98/109 x 100% = 89% BW/H: 23/15 x 100% = 153%       . At first the swollen part began in the face. without sputum and the patient did not have shortness of breath. Patient’s mother realized that the patient has been experiencing this approximately 5 days ago. Physical Examination Body weight Height LPT LLA : 23 kg : 98 cm : 74 cm : 6. Patient's urine was in a yellowish color. The midwife said this was just an overweight process and patient’s mother forgot about the patient’s weight gain. The patient’s mother brought him to a midwife.      Name Age Sex Date of Admission :MH : 5 years old : Male : November. The patient also had cough for 2 days. No sandy urination. The patient then regularly checks up on his condition at Adam Malik General Hospital. both arms and legs.     History of previous illness:The patient has already finish medication of prednisone in the previous hospital and had his condition control routinely every month but no improvement was seen and proteinuria keeps increasing.5 cm IBW: 15. 8th 2013 Main complaint: Swollen on the whole body.

HR: 40 tpm.Nephrotic Syndrome Steroid Resistance : O2 nasal canule 1 L/i three way attached IVFD D5 % 4 gtt/i micro Furosemide 2x20 mg inj Ceftriaxone 500 mg/12 hours -> skin test Paracetamol 3x250 mg prednisone 3-2-2 tab/day -> once every 2 days . Working Diagnosis : Lymph node enlargement (-) : Icteric (-) Symmetrical fusiformis. Body temperature: 38oC. icteric (-/-) . conjunctiva palpebra inferior anemia (-/-). Respiratory Rate: 44 tpm. warm : Nephrotic Syndrome Steroid Resistance          Diffential Diagnosis Medication : . adequate pressure and volume. murmur (-). symmetrical. Pain(-).            Presence status Sens. Nose: Normal appereance. Neck Thorax Abdomen Extremities extremities. Crackles (-/-) : Distention (+). Ear : Normal appereance Mouth :Sianosis (-). Compos Mentis. Liver/Spleen : Unidentified : Pulse 140 bpm. Acites (+). HR:140 bpm. isochoric pupil. Pulse: 140 bpm. Decreased tenderness. Epigastria retraction (-). CRT< 3”. regular. regular. regular. Peristaltic difficult to assess. Localized status Head : Normocephalic Eye : Light reflexes(+/+).

0 106 19 .1 3.7-17.6-5.20 0.60 555 76.50 0.0 18.Laboratory Result: November 8th 2013 Complete blood count(CBC) Hemoglobin (HGB) Eritrosit (RBC) Leukosit (WBC) Hematokrit Trombosit (PLT) MCV MCH MCHC RDW WBC Count Neutrofil Limfosit Monosit Eosinofil Basofil Unit Value Normal value g% 106/ mm3 103/ mm3 % 103/ fL Pg g% % % % % % % mm3 9.00 20.80 11.5 38-52 217-497 93-115 29-35 28-34 14.17.85 135-155 3.1 Carbohydrate metabolism Glukosa ad random Renal Ureum Kreatinin Electrolytes Natrium (Na) Kalium (K) Klorida (Cl) Mg/dl Mg/dl Mg/dl mEq/L mEq/L mEq/L 169.7 37 – 80 20 – 40 2–8 1–6 0–1 67.70 20.50 25.61 30.9-18.80 33.30 3.0.36 <200 <50 0.670 27.24-0.50 10.90 2.75-4.95 6.5 96-106 136 4.

HR: 118 bpm. thursday. regular. Epigastria retraction (+). adequate pressure and volume. isochoric pupil diameter of right pupil = 3mm .IVFD D5% 4 gtt/i micro .Ceftriaxone 1 gr/ 12 hours/ iv . symmetrical. saturday) . regular.icteric (-/-) . warm acral. RR: 24 bpm. Liver&Spleen: unidentified Extremities: Pulse 118 bpm.FOLLOW UP Date November 8th -10th 2013 S: Swollen on the whole body (-) . Cough (-) O: Sens: CM Temp: 36.Ampicillin 1 gr/ 8 hr/ iv . CRT< 3” Diagnosis Management Nephrotic Syndrome Steroid Resistance -O2 nasal canule ½ L/i (November 8-9th) .6oC Head : Moon face (+) Normosefali Eye : Light reflexes(+ /+). Peristaltic(difficult to assess).Three way attached .Low salt diet 1800 kcal and 45 gr protein Plan : -Urinalysis 20 . Nose: normal appeareance (+). Ear : Normal appereance . murmur (-). Crackles (-/-) Abdomen: Soepel. conjunctiva palpebra inferior anemic (+/+).Mouth : Sianosis (-). Nasal flare (-) Neck : Lymph node enlargement (-) nuchal rigidity (-) Thorax : Symmetrical fusiformis. left pupil = 2 mm.inj furosemide 20 mg / 8 hours/ iv .prednisone alternating dose 1x6 tab -> morning (tuesday.

0 +3 Yellow 1.005-1.020 5.030 5-8 - Nitrit Blood Sedimen Eritrocyte Leukocyte Epithel Cast Crystal - - 0-1 1-2 0-1 Granular 1-3 - <3 <6 - .Laboratory Result: November 9th 2013 Urinalysis Colour Glucose Bilirubin Keton Density pH Protein Urobilinogen Turbid Yellow 1.

Aldacton 2x12. regular. Epigastria retraction (+).Bicnat tab 4-3-3 .6oC Head : Moon face (+) Normosefali Eye : Light reflexes(+ /+). Nasal flare (-) Neck : Lymph node enlargement (-) nuchal rigidity (-) Thorax : Symmetrical fusiformis. Liver&Spleen: unidentified Extremities: Pulse 118 bpm.Furosemide inj. 30 mg/ 8 hours IV . conjunctiva palpebra inferior anemic (+/+). Nose: normal appeareance (+).prednisone 1x6 tab (morning) .5 mg . murmur (-). Peristaltic(difficult to assess). left pupil = 2 mm. isochoric pupil diameter of right pupil = 3mm . Cough (-) O: Sens: CM Temp: 36.Low Salt Diet 1700 kkal with 30 gr of protein .icteric (-/-) . adequate pressure and volume. symmetrical.Fluid balance 22 .Mouth : Sianosis (-).ceftriaxone inj 1 gr / 12 hr / iv . regular.Date November 11th -13th 2013 S: Swollen on the whole body (-) . HR: 118 bpm. Crackles (-/-) Abdomen: Soepel.Ampicillin 1 gr/ 12 hr/ iv . Ear : Normal appereance . CRT< 3” Diagnosis Nephrotic Syndrome Steroid Resistance Management : . warm acral. RR: 24 bpm.

2 3.8-5.77 9.6-5.2 3.Laboratory Result: November 12th 2013 Hati Albumin Elektrolit Calsium (Ca) Natrium (Na) Kalium (K) Klorida (Cl) Magnesium (Mg) mEq/L mEq/L mEq/L mEq/L mEq/L 6.4 .9 g/dL 1.2-11.5 96-106 1.0 135-155 3.8-5.4 136 3.4-1.4 Hati Albumin g/dL 1.9 106 1.

3 22.7 37 – 80 20 – 40 2–8 1–6 0–1 Blood gas analysis pH pCO2 PO2 Bikarbonat (HCO3) Total CO2 Kelebihan basa (BE) Saturasi O2 Electrolytes Natrium (Na) Kalium (K) Klorida (Cl) mEq/L mEq/L mEq/L 132 3.5 Hematokrit Trombosit (PLT) MCV MCH MCHC RDW WBC Count Neutrofil Limfosit Monosit Eosinofil Basofil % 103/ fL Pg g% % % % % % % 26.0.9-18.7 101 135-155 3.6-5.50 25.7 -1.4 0.24 10.2 38-52 217-497 93-115 29-35 28-34 14.7-17.5 7.44 12.80 10.80 3.50 18.30 429 79.0 99.70 61.70 26.60 33.90 0.452 mmHg mmHg mmol/L mmol/L mmol/L % 33.75-4.95 6.45 38-42 85-100 22-26 19-25 (-2)-(2) 95-100 24 .November 13th 2013 Complete blood count(CBC) Hemoglobin (HGB) Eritrosit (RBC) Leukosit (WBC) g% 106/ 103/ mm3 mm3 mm3 8.5 96-106 7.35-7.7 23.1 3.2 172.17.

Crackles (-/-) Abdomen: Soepel. symmetrical. 40 mg/ 8 hours IV .Date November 14th -16th 2013 S: Swollen on the whole body (-) .6oC Head : Moon face (+) Normosefali Eye : Light reflexes(+ /+). HR: 118 bpm.Ceftriaxone inj 1 gr/ 12 hr/ IV . Liver&Spleen: unidentified Extremities: Pulse 118 bpm. isochoric pupil diameter of right pupil = 3mm . adequate pressure and volume. Nose: normal appeareance (+). RR: 24 bpm. warm acral. Nasal flare (-) Neck : Lymph node enlargement (-) nuchal rigidity (-) Thorax : Symmetrical fusiformis.Mouth : Sianosis (-).Ampicillin inj 1 gr/ 8 hr/ IV . Ear : Normal appereance . conjunctiva palpebra inferior anemic (+/+). regular. left pupil = 2 mm. murmur (-). regular. Diagnosis Nephrotic Syndrome Steroid Resistance Management . CRT< 3”.Prednisone inj 1x6 tab (morning) .Aldacton 2x12. Cough (-) O: Sens: CM Temp: 36.Ambroxol 3x3 mg 25 . Epigastria retraction (+).Furosemide inj.5 mg . Peristaltic(difficult to assess).icteric (-/-) .

10 17.20 10.00 15.1 3.00 3.50 1.4 26 .7.70 33.90 46.7-17.Phenytoin oral 2x 6 mg .Head elevation 30 degree .75-4.8-5.3 3.Cefadroxil syp 3 x 100 mg .70 25.3 103/µL Hati Albumin g/dL 1.4 .67 37 – 80 20 – 40 2–8 1–6 0–1 2.5 38-52 Trombosit (PLT) MCV MCH MCHC RDW  A: Vitamin K deficiency bleeding 640 + subdural 217-497 103/ mm3 fL      WBC Count Neutrofil Limfosit Monosit Eosinofil Basofil hemorrhage P: .50 11.17.9-18.25 27.95 6.Laboratory Result: November 16th 2013 Complete blood count(CBC) Hemoglobin (HGB) Eritrosit (RBC) Leukosit (WBC) Hematokrit g% 106/ mm3 103/ mm3 % 9.7 36.30 0.3 2.0.Diet 40 cc/ 2 hours / oral Pg g% % % % % % % 77.60 93-115 29-35 28-34 14.

5 mg . RR: 24 bpm. Peristaltic(difficult to assess). Cough (-) O: Sens: CM Temp: 36. isochoric pupil diameter of right pupil = 3mm .IVFD albumin 20% = 23/20 x 100 : 115 cc 27 . murmur (-). CRT< 3” Diagnosis Nephrotic Syndrome Steroid Resistance Management . Nose: normal appeareance (+).Furosemide inj. Nasal flare (-) Neck : Lymph node enlargement (-) nuchal rigidity (-) Thorax : Symmetrical fusiformis.Date November 17th -18th 2013 S: Swollen on the whole body (-) . warm acral.icteric (-/-) . conjunctiva palpebra inferior anemic (+/+).Prednison alternating dose 1x6 tab (morning) .Ambroxol 3x3 . left pupil = 2 mm. symmetrical. Crackles (-/-) Abdomen: Soepel. Ear : Normal appereance .6oC Head : Moon face (+) Normosefali Eye : Light reflexes(+ /+). Epigastria retraction (+).Mouth : Sianosis (-). regular. Liver&Spleen: unidentified Extremities: Pulse 118 bpm. adequate pressure and volume.Ceftriaxone inj 1 gr/ 12 hr/ IV . 40 mg/ 8 hours IV .Aldacton 2x12.Ampicillin 1 gr/ 12 hr/ iv . HR: 118 bpm. regular.

♂:♀= 2:1 penderita adalah anak laki-laki usia 5 tahun 3 bulan dengan keluhan utama bengkak pada seluruh tubuh. pemeriksaan proteinuria +3 dan kadar albumin rendah 28 .DISKUSI SN Kasus • proteinuria masif ( 40 mg/m2LPB/jam atau proteinuria dipstik  2+) • hipoalbuminemia ( 2.5 g/dL) • edema • hiperkolesterolemia (kolesterol serum > 200 mg/dL) • Puncak kejadian : usia 2-3 tahun .

lamanya pengobatan & manfaat diet • Penderita telah diberikan terapi kortikosteroid yaitu prednison dengan dosis 2 mg/kgBB/hari selama 3 bulan • pasien tidak patuh terhadap regimen pengobatan • orangtua yang tidak mampu memotivasi anaknya 29 .SN Kasus • Pengobatan  belum memuaskan • 10% respon anak gagal induksi • Edukasi  perjalanan penyakit. komplikasi.

Rabu dan Jumat. 30 .• Remisi (-) selama 4 minggu terapi steroid inisial SNRS • Prednison dosis 40 mg/m2LPB/hari kelang sehari selama pemberian CPA puls dengan dosis 500 sampai 750 mg/m2LPB/bulan selama 6 bulan. kemudian dosis prednison diturunkan menjadi 1 mg/kg/hari selama 1 bulan dilanjutkan dengan 0. diberikan prednison 2/3 dosis awal selang sehari yaitu diberikan pada hari Senin.5 mg/kg/hari selama 1 bulan berikutnya Kasus • Penderita di-diagnosis sebagai SNRS.

SNRS Kasus • Dalam prakteknya. namun mereka langsung mendapat terapi empiris kortikosteroid • Pada kelainan histologis dengan prognosis buruk perlu dilakukan biopsi ginjal • Penderita langsung mendapat terapi prednison secara empiris tanpa melakukan pemeriksaan biopsi ginjal 31 . sebagian besar anak tidak menjalani biopsi ginjal pada manifestasi klinis SN pertama kali.

KORTIKOSTEROI D Efek anti-inflamasi  melalui penekanan pembentukan berbagai mediator inflamasi. mobilisasi asam amino (sebagai substrak untuk glukoneogenesis) dan menghambat ambilan glukosa di otot serta jaringan adipose-> menumpuk. menghambat fungsi makrofag dan bekerja dalam inflamasi akut maupun kronik 32 . lipolisis.Efek metabolisme  proses glukoneogenesis di hati.

dagu ganda dan dapat dijumpai adanya buffalo hump.Tanda klinis Sindrom Cushing : obesitas dengan letak lemak sentripetal  bentuk wajah bulat. paha. dijumpai tanda-tanda klinis sepertiobesitas dengan letak lemak sentripetal  bentuk wajah bulat. dagu ganda dan dapat dijumpai adanya buffalo hump  Kulit tipis disertai stria ungu pada abdomen. bokong dan lengan atas Kulit mudah mengalami memar dan terinfeksi jamur Penunjang diagnostik Sindrom Cushing : Peningkatan kadar kortisol bebas dalam urin 24 jam Pemeriksaan kadar kortisol plasma  >3 tahun  Pada kasus. 33 .  pemeriksaan kortisol tidak sempat dilakukan karena pasien pulang.