Nephrotic syndrome case presentation

A case study presentation of child nephrotic syndrome at BPKIHS,DHARAN.

1. A CASE STUDY Moderator Dr. Jouslin k Baranwal Asst. Prof Department of Biochemistry, BPKIHS Presenter Binaya Tamang MSc. 3 rd year Department of Biochemistry , BPKIHS

2. History Name: Rhythm Rai Age: 2.5 years Sex: Male Religion: Hindu From: Chulachuli Patient Id:2724478 On 74/ 2/18, 4: 05 PM Reported to the pediatric emergency with the chief complains of Generalized swelling of the body X 5 days . Swelling started from the face followed by swelling of abdomen , upper and lower limbs. No h/o of rash , fever, sore throat, fast breathing Patient was taken to the local hospital and some medicine was given, a USG was done and referred to BPKIHS.

3. History of Present Illness The patient was apparently well 5 days back when his mother noticed swelling of her face, which was acute in onset and gradually progressing towards the abdomen and bilateral upper and lower limbs. The swelling is painless and pitting in nature. The overlying skin was normal and there is no history of itching and rashes. No h/o frothy urine ,yellowish discoloration of urine No h/o cough, chest pain No h/o abdominal pain, loss of appetite, vomiting. No h/o fever , joint pain , photosensitivity and oral ulcers

4. Contd ,,, No h/o altered bowel habit and bladder No h/o passage of frank blood in the urine No h/o crying at micturition , yellowish discoloration of the body No h/o any skin infection No h/o petechia , purpura .

5. Past history: h/o throat infection 2-3 months back No h/o of similar illness No h/o TB, asthma, HTN, DM No h/o fever with rash, neck swelling. Antenatal: No any ANC visits No TT vaccines No iron and calcium taken No h/o fever, rashes, lymphadenopathy No h/o excessive vomiting, increased frequency of micturition No h/o burning micturition, increased urgency No h/o PV bleeding, spotting No h/o headache, blurring of vision, epigastric pain . Perinatal history: Normal term, spontaneous vaginal delivery at ( patient not sure of exact date) Baby cried at birth. Baby weight:-2.0 kg Breast feeding at 4 hours of life . Post natal history: No h/o Excessive bleeding No other complications

6. Family history: No h/o similar illness in family No h/o consanguineous marriage No h/o TB, DM, Kidney deases No h/o HTN Dietary History : Tea+ 1 kotori rice+ 1 kotori daal + 1 kotori potato curry Not significant history given by mother . Immunization history: Immunization as per EPI schedule with strictly all vaccines given to child Developmental History H/o normal developments Explore drawers, runs ups and downstairs Vertical and circular strokes Asks for food , toilets 2-3 word sentence, short sentences

7. On Examination General condition : facial puffiness + ve Edema + ve , bilateral pitting edema of limbs No any scar marks of infection Vitals Pulse: 110/min; regular, normal vol and character, RR: 22/min Temp: 98 F BP: 90/60 on rt arm in sitting position GPE Pallor Icterus Lymphadenopathy Cyanosis Dehydration Anthropometry Weight: 13.5 kg

8. GIT: Abdomen distended, umbilicus central, all quadrant moving symmetrically with respiration, no venous prominence, no scar marks, hernia site are intact. On palpation: no local rise in temp no tenderness no any lump and organ On percussion: shifting dullness present Chest: Bilateral Equal Chest Expansion;B /L Normal vesicular breath sounds ; no added sounds, Trachea Central CVS : S1S2,Mo, No added sounds. Preliminary Diagnosis. Probably a case of nephrotic syndrome. Mostly Minimal change Disease ( as per incidence and geography).

9. Investigation Biochemical Parameters Parameters Result Reference range UREA 14mg/dl 10-50 Creatinine 0.2mg/dl 0.5-1.4 Sodium 131 mmol /L 136-145 Potassium 4.1mmol/L 3.5-5.0 Total Protein in 24 hrs urine 360 ml/ 0.27 g/day 1500-2500 <0.15 Serum cholesterol(Total) 423 mg/dl <200 Serum albumin 2.3 g/dl 3.5-5.3 Urinary protein creatinine ratio 0.51 3.06 <0.2mg/g

10. Contd …. Urine RE Result Albumin 4+ Sugar Nil Microscopic Test WBCs 2-3/HPF RBCs 8-10/HPF Epithelial cells 3-5/HPF Others not seen. Urine culture and sensitivity Sterile after 24 hours. HBsAg , HCV and HIV negative Sputum AFB : not seen.

11. Hematological parameters. Parameters Result Reference Blood group O positive CBC Hemoglobin 12.8 gm/dl 11-16gm/dl PCV 35.9 36-48% TLC 9400 4000-11000 cell/mm cu Neutrophil 25 40-75 % Lymphocyte 60 20-45% Monocyte 06 2-10% Eosinophil 09 1-6% Platelet 324000 150000-400000cell/mm cu ESR 54 1 st hour

12. Final Diagnosis With the clinical sign and symptoms , lab diagnosis, age as well as other no secondary diseases associated. Nephrotic syndrome with some hematuria. Most probably minimal change disease nephrotic syndrome for the confirmation renal biopsy is preferred. Most (>85%) of children MCN.

13. Treatment Given : Sryp Ritocef (5/50) 5ml x PO x BD Tab Emsolone 25 mg x PO X OD Orally allowed Sryp Digene 5ml x PO x BD

14. Glomerular Membrane Modified capillary wall comprising endothelium ( 50-100 nm pores) A cell-less basement membrane and an outer specialized epithelial cell layer ( 55 nm slit diaphragm) The whole of the glomerular membrane carries a fixed net negative charge: Due to a Glycosialoprotein coat Charge increases in density from the Lamina Interna towards the Lamina rara Externa with the greatest density at the slit diaphragm of the epithelium

15. Adapted from : Notes For USMLE

16. Nephrotic Syndrome It is a common glomerular disease, characterized by nephrotic range proteinuria and a triad of clinical findings associated with large urinary losses of protein : hypoalbuminaemia , edema and hyperlipidemia It is clinical face of glomerular injury. Why ‘nephrotic range’ Defined as protein excretion of > 40 mg/m 2 / hr and >3.5 gm/day.

17. Incidence ( paediatric ) ? 2 – 7 cases per 100,000 children per year Higher in underdeveloped countries ( South east A sia ) 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 http://www.kidney.org/site/107/pdf/NephroticSyndrome.pdf

18. Etiology Genetic Secondary Idiopathic or Primary

19. Types of nephrotic syndrome Causes prevalence(%) children adults Primary glomerular diseases Membranous nephropathy 3 30 Minimal change disease 75 8 Focalsegmental glomerulosclerosis 10 35 Membranoproliferative glomerulonephritis and dense disease 10 10 Other proliferative glomerulonephritis(focal, pure mesangial , IgA nephropathy 2 17 Systemic Disease Diabetes mellitus, amyloidosis, systemic lupus erythematous Drugs ( NSAIDS, penicillamine , heroin), infection ( malaria, syphilis, hepatitis B and C, HIV), Malignant disease ( carcinoma, lymphoma), Miscellaneous ( bee-sting, hereditary nephritis)

20. Pathophysiology :- Minimal change disease This relatively benign disorder is characterized by diffuse effacement of foot processes of visceral epithelial cells( podocytes ), detectable only by electron microscope, appear virtually normal by light microscope. It is the most common cause of nephrotic syndrome in children(2-6 years) Pathogenesis: idiopathic but current leading hypothesis involves some immune dysfunction that results in the elaboration of factors that damage visceral epithelial cells and cause proteinuria. Animal model=angiopoietin –like-4 but not have been proven to cause in human. Primary visceral epithelial cell injury ( podocytopathy ) and loss of polyanions . Protein traverse capillary wall remains enigma . http://www.highlands.edu/academics/divisions/scipe/biology/faculty/harnden/2122/images/renalcorpuscle.jpg

21. Complex disturbances in immune system Genetic Mutations / Mutations in proteins Extensive effacement of podocyte foot processes Increased permeability of the glomerular capillary wall Massive proteinuria Hypoalbuminaemia Edema

22. How changes occurs? The glomerular capillary wall, with its endothelium , GBM and visceral epithelial cells, acts as size and charge barrier through which plasma filter passes. Increased permeability from either structural and physiochemical alterations in this barrier allows proteins to escape from plasma in to urine  proteinuria. Heavy proteinuria depletes serum albumin level at rate beyond the compensatory synthetic capacity of liver hypoalbunemia

23. The generalized edema is a direct consequence of decreased intravascular colloid osmotic pressure . There is also sodium and water retention, which aggravates the edema. Several factors including compensatory secretion of aldosterone mediated by hypovolemia-enhanced renin secretion ; stimulation of sympathetic system ; and a reduction in the secretion of natriuretic factors such as atrial peptides Edema ; soft and pitting, and is most marked in periorbital regions. The genesis of the hyper lipidemia is complex. Increased synthesis of lipoproteins in the liver Abnormal transport of circulating lipids particles Decreased lipid catabolism. Finally lipiduria seen as oval fat bodies.

24. Clinical features Edema Mild to start with – peri orbital puffiness, lower extremities Progression to generalized edema, ascites, pleural effusion, genital edema Decreased urine output Anorexia, Irritability, Abdominal pain and diarrhea Absence of Hypertension Gross hematuria

25. Vulnerable of Infection , especially staphylococcal and pneumococcal infection probably due to loss of immunoglobulins. Thrombotic and thromboembolic complication : antithrombin III Anemia due to loss of transferrin.

26. Lab Investigations Urine Examination Complete Blood Count & Blood picture Renal parameters : Spot Urine Protein : Creatinine ratio Urinary protein excretion protein selectivity ratio Liver Function Test Renal Biopsy ??? Urinalysis - 3+ to 4+ proteinuria Renal Function Spot UPC ratio > 2.0 UPE > 40 mg/m 2 / hr Serum Creatinine – normal or elevated Serum albumin - < 2.5 gm/dl Serum Cholesterol/ TGA levels – elevated Serum Complement levels – Normal or low

27. Additional Tests C3 and antistreptolysin O Chest X ray and tuberculin test ANA Hepatitis B surface antigen Genetic analysis Ghai Essential Paediatrics,8 th edition, page 478 Indications for Biopsy Age below 12 months Gross or persistent microscopic hematuria Low blood C3 Hypertension Impaired renal Function Failure of steroid therapy

28. Management High protein diet Salt moderation Treatment of infections If significant edema – diuretics Aldosterone antagonist ( Fursemide , spironolactone ) Corticosteroid therapy with Prednisolone or prednisone ( 2mg/kg per day for 6 weeks followed by 1.5 mg/kg single morning dose on alternate days for 6 weeks ) Ghai Essential Paediatrics,8 th edition, page 476, 477

29. Complications Edema Infections Thrombotic complications Hypovolemia and Acute renal Failure Steroid Toxicity Ghai Essential Paediatrics,8 th edition, page 480, 481

30. Parent education. Should be explained about diseases and the usual outcomes Their cooperation is ensured If possible they are taught how to examine urine for protein, Which should be done periodically to detect relapse early.