NEPHROTIC SYNDROME In children in short.

Here’s a summary of Nephrotic Syndrome (from standard medical sources like Harrison’s, Nelson’s, and Davidson’s):


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Nephrotic Syndrome – Summary

Definition:
Nephrotic syndrome is a clinical complex characterized by heavy proteinuria (>3.5 g/day in adults or >40 mg/m²/hr in children), leading to hypoalbuminemia, edema, hyperlipidemia, and lipiduria.


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Pathophysiology:

Damage to glomerular filtration barrier (podocytes, basement membrane, endothelium) → increased permeability to plasma proteins.

Loss of albumin in urine → decreased plasma oncotic pressure → edema.

Liver compensates by increasing lipoprotein synthesis → hyperlipidemia.

Loss of regulatory proteins (antithrombin III, IgG, etc.) → ↑ risk of thrombosis and infections.



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Etiology:

1. Primary (Idiopathic) Glomerular Diseases:

Minimal change disease (common in children)

Focal segmental glomerulosclerosis (FSGS)

Membranous nephropathy

Membranoproliferative GN


2. Secondary Causes:

Diabetes mellitus (diabetic nephropathy)

Systemic lupus erythematosus (SLE)

Amyloidosis

Infections (Hepatitis B, C, HIV, malaria)

Drugs (NSAIDs, gold, penicillamine)



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Clinical Features:

Generalized edema (starting as periorbital, then pitting edema, ascites, pleural effusion)

Frothy urine (due to proteinuria)

Weight gain

Fatigue, pallor

Complications:

Infection (due to loss of IgG, complement)

Thrombosis (renal vein, DVT, PE)

Hypovolemia, acute kidney injury




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Investigations:

Urinalysis: Proteinuria, lipiduria (fat bodies, Maltese crosses)

24-hour urine protein / Spot protein:creatinine ratio

Serum albumin: ↓

Serum cholesterol & triglycerides: ↑

Renal function tests: May be normal or mildly abnormal

Renal biopsy: To determine underlying cause (except in typical minimal change disease in children)



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Management:

1. General Measures:

Salt restriction

Diuretics (for edema)

Adequate protein intake (not excessive)

Control hyperlipidemia (statins)

Anticoagulation if thrombosis risk high

Vaccination (pneumococcal, influenza)


2. Specific Treatment:

Minimal Change Disease: Corticosteroids (Prednisolone)

FSGS, Membranous GN: Steroids ± immunosuppressants (cyclophosphamide, cyclosporine, tacrolimus)

Secondary causes: Treat underlying disease (e.g., control diabetes, treat infection, stop offending drug)



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Prognosis:

Children: Usually good (especially minimal change disease).

Adults: Depends on cause — FSGS and membranous nephropathy may progress to chronic kidney disease.



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Would you like me to make this into a chart or table format (easy for revision or presentation)?

1. NEPHROTIC SYNDROME Presented by f Batch [126-150]

2. Definition Etiology Clinical features Terminologies

3. definition NEPHROTIC SYNDROME IS CHARACTERISTICALLY DEFINED BY PRESENCE OF THREE PRIMARY FEATURES- 1. massive PROTEINURIA ( >1g/m2/day) 2. HYPOALBUMINEMIA ( sr alb <3g/dL) 3. EDEMA 4. HYPERCHOLESTEROLEMIA

4. PROTEINURIA AND HYPOALBUMINEMIA PROTEINURIA IN CHILDREN IS DEFINED BY >4mg/m 2 /h OR >100mg/m 2 /24h NEPHROTIC RANGE OF PROTEINURIA IS ABLOVE >40mg/m 2 /h OR >1000mg/m 2 /24h SERUM ALBUMIN LEVELS <3mg/dL

5. eTIOLOGY DISTURBANCE IN GLOMERULAR FILTRATION BARRIER. LEADS TO LOSS OF LARGE AMOUNT OF ALBUMIN IN URINE. 90-95% CASES FALL IN PRIMARY (IDIOPATHIC) PATHOLOGY. SECONDARY CAUSES CAN BE IDENTIFIED IN APPROX. 10-15% CASES. CLASSIFICATION BASED ON ETIOLOGY – PRIMARY vs SECONDARY CLASSIFICATION BASED ON AGE OF ONSET – CONGENITAL vs INFANTILE CLASSIFICATION BASED ON HISTOLOGY – MCD vs NEPHROTIC SYNDROME WITH SIGNIFICANT LESIONS

6. Primary nephrotic syndrome MINIMAL CHANGE DISEASE [MCD] 80%CASES. FSGS (2 nd MOST COMMON CAUSE) MesPGN MGN MPGN

7. SECONDARY NEPHROTIC SYNDROME SYSTEMIC CONDITIONS - SLE, HSP, SCA, HODGKIN’S LYMPHOMA, AMYLOIDOSIS, ETC. INFECTIONS - HIV, PARVOVIRUS B19, HEPATITIS B, HEPATITIS C, SYPHILIS INTRAUTERINE INFECTIONS - SYPHILIS, CMV. DRUGS- NSAIDS, PENICILLAMINE, GOLD TOXINS OR ALLERGENS (BEE STING) ENDOCRINE- DM *DETAILED EVALUATION INCLUDES BIOPSY MAYBE REQUIRED FOR THE ESTABLISHMENT OF THE DIAGNOSIS IN SOME CASES.

8. Classification based on age of onset CONGENITAL INFANTILE FAM HISTORY +++ (NPHS1= finnish type; NPHS2=non finnish type) --- AGE OF ONSET <3 MONTHS 3-12 MONTHS PLACENTA LARGE NORMAL COMPLEMENT REDUCED NORMAL IgM Ab RAISED NORMAL HISTOLOGY MCD (mc) VARIABLE CAUSES CONGENITAL INFECTIONS IDIOPATHIC PROGNOSIS POOR VARIABLE

9. CLASSIFICATION BASED ON HISTOLOGY MCD SIGNIFICANT LESIONS INCIDENCE >85% <15% AGE OF ONSET 2-6 yrs <2 or >6 yrs SEX M > F M = F HEMATURIA --- +++ LESION MCD FSGS > MesPGN , MPGN, MGN PATHOLOGY PODOCYTOPATHY COMPLEMENT ACTIVATION AND IMMUNE COMPLEX DEPOSITION C3 NORMAL REDUCED PROTEINURIA ALBUMIN (majority) ALBUMIN = LMW PROTEINS RESPONSE TO STEROID +++++++ -- COMPLICATIONS -- ++ PROGNOSIS GOOD FAIR TO POOR

10. PATHOGENESIS TRIGGER / URTI  Th2  IL-4, IL-10, IL-13  BIND TO RECEPTORS ON PODODCYTES  EFFACEMENT OF FOOT PROCESSES  GLOMERULAR FILTRATION BARRIER DISRUPTION  HYPOALBUMINEMIA LOSS OF IgG  INFECTIONS; LOSS OF ANTITHROMBIN III  THROMBOSIS HYPOALBUMINEMIA  FALL IN PLASMA ONCOTIC PRESSURE  FLUID SHIFT FROM INTRAVASCULAR TO INTERSTITIAL COMPARTMENT  RAAS  EDEMA, HTN LIVER WILL COMPENSATES THE LOSS OF LDLr [LIPOPROTEINS] IN URINE  INCREASED LIPOPROTEIN SYNTHESIS  HYPERCHOLESTEROLEMIA.

11. CLINICAL FEATURES PERIORBITAL PUFFINESS  PROGRESSION OF EDEMA  ANASARCA NECK EDEMA, PLEURAL EFFUSION, ASCITES, SCROTAL/PENILE/VULVAL OR PEDAL EDEMA. SACRAL EDEMA IN CASE OF BED-RIDDEN PATIENT. EDEMA WILL BE PITTING, a/w OLIGURIA. MILD HTN IS COMMON DUE TO RAAS ACTIVATION. *PERSISTENT OR SEVERE HTN GENERALLY POINTS TOWARDS NON-MCD.

12. COMPLICATIONS SERIOUS INFECTIONS (d/t IgG loss)- SBP, CELLULITIS, PNEUMONIA, OR UTI. THROMBOEMBOLIC COMPLICATIONS (d/t loss of protein C, S, antithrombin III)- CEREBRAL OR RENAL THROMBOSIS HYPOVOLUMIC SHOCK (d/t fluid redistribution)  AKI  RENAL FAILURE ANEMIA (d/t loss of transferrin) HYPOTHYROIDISM (d/t loss of thyroid binding globulin) HYPOCALCEMIA (d/t loss of vit D binding globulin)  CONVULSIONS ZINC AND COPPER DEFICIENCY (d/t loss of metal binding proteins) ACCELERATED ATHEROSCLEROSIS (d/t a state of chronic inflammation)

13. IMPORTANT TERMINOLOGIES STEROID SENSITIVE CASE: Disappearance of clinical and biochemical features w/in 8 weeks of starting steroid therapy. STEROID RESISTANCE: No remission after oral prednisolone 2mg/kg/day for 4 weeks OR, persistent proteinuria after completion of treatment. STEROID DEPENDENT CASES : 2 consecutive relapses during steroid therapy or within 2 weeks of stopping the therapy.

14. IMPORTANT TERMINOLOGIES REMISSION: Ur alb <4mg/m2/ hr (or nil/trace on dipstick) + sr alb >3.5g/dL + no edema RELAPSE: Ur alb >3+ on dipstick for 3 days + proteinuria >40 mg/m2/ hr for 3 consecutive samples. FREQUENT RELAPSE : >2 ep of relapse within 6 months after stopping the treatment OR, >4 ep in any 12 month period. INFREQUENT RELAPSE: 1 ep of relapse in 6 months OR, <3 ep in 12 months.

15. QUESTIONS

16. Which is not a common cause of nephrotic syndrome? FSGS PSGN MCD MPGN

17. B) PSGN

18. A 4y/o boy came with c/o frothy urine and painful micturition. On examination there is edema. UPCR on spot urine sample is 3mg/g. Diagnosis? Dehydration proteinuria Orthostatic proteinuria Nephrotic syndrome It’s just a cute baby

19. c) Nephrotic syndrome

20. A 9 y/o is diagnosed as a case of nephrotic syndrome. Renal biopsy was performed, indicated by hematuria. On histology, the pathologist ruled out MCD as significant glomerular lesions were present. What lesion did the pathologist most likely see? MesPGN FSGS MPGN MGN

21. b) fsgs Factors favouring the diagnosis – age >6 years, hematuria++, FSGS is the mcc of nephrotic syndrome due to significant glomerular lesions

22. What gene mutation is not implicated in the pathogenesis of nephrotic syndrome? NPHS1 NPHS2 WT1 SCN1A

23. D) SCNIA NPHS1 – nephrin gene, on chr 19 NPHS2 – podocin gene, on chr 1 WT1 – WAGR, Wilms tumor, nephrotic syndrome on chr 11 SCN1A – voltage gated Na channels, Dravet syndrome, on chr 2

24. What is not seen in nephrotic syndrome? Proteinuria Hypoproteinemia Edema Hypercholesterolemia

25. x) Trick question All can be seen in nephrotic syndrome but HYPERCHOLESTEROLEMIA IS NO LONGER A DIAGNOSTIC CRITERION

26. REFFERENCES GHAI TEXTBOOK OF PEDIATRICS UG TEXTBOOK OF PEDIATRICS BY PIYUSH GUPTA CLINICAL PAEDIATRICS BY ARUCHAMY LAKSHMANSWAMY

27. THANK YOU