Nephrotic Syndrome — Short Answer Questions (NEET-PG / INICET)

SAQ 1 — Define nephrotic syndrome and state the commonest cause in children and in adults

Define (the tetrad — reproduce verbatim): [1]

1. Heavy proteinuria — over 3.5 g/day (or over 50 mg/kg/day, or a spot urine protein-to-creatinine ratio over 300 mg/mmol / over 2 g/g).
2. Hypoalbuminaemia — serum albumin under 30 g/L (often under 25 g/L).
3. Oedema — periorbital (morning) and dependent.
4. Hyperlipidaemia and lipiduria — raised cholesterol/LDL; oval fat bodies with a "Maltese-cross" under polarised light. [1]

Commonest cause: Children — minimal change disease (~75-90%, peak 2-6 years, steroid-responsive). Adults — membranous nephropathy and FSGS (primary), with diabetic nephropathy the commonest secondary cause overall. [1]

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SAQ 2 — A 45-year-old man with nephrotic syndrome develops sudden left flank pain and haematuria. Discuss the likely diagnosis, the mechanism, and the management

Diagnosis: Renal vein thrombosis — sudden flank/loin pain, haematuria and a rising creatinine in a nephrotic patient (risk is highest in membranous nephropathy). [1]

Mechanism (hypercoagulable state):

• Urinary loss of antithrombin III (the key inhibitor of thrombin).
• Increased hepatic fibrinogen and factor VIII synthesis.
• Platelet activation, hemoconcentration and hyperviscosity. [1]

Management:

• Image with renal Doppler ultrasound or CT venography to confirm.
• Anticoagulate (heparin → warfarin, or a DOAC) for at least the duration of nephrotic-range proteinuria.
• Prophylactic anticoagulation should be considered in nephrotic patients when albumin is under 25-30 g/L, especially in membranous nephropathy. [1]

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SAQ 3 — Outline the investigations and the role of renal biopsy in nephrotic syndrome

Confirm and quantify: dipstick (4+ protein), 24-h urine protein (over 3.5 g/day) or spot urine protein-to-creatinine ratio (over 300 mg/mmol), serum albumin (under 30 g/L), renal function, lipid profile, urine microscopy (oval fat bodies / Maltese cross = lipiduria). [1]

Classify the cause (serology): ANA, anti-dsDNA, complement (C3/C4) (lupus); HBsAg, anti-HCV, HIV; serum electrophoresis and serum free light chains (myeloma/AL amyloid); anti-PLA2R antibody (primary membranous nephropathy). [1]

Renal biopsy: indicated in all adults with nephrotic syndrome, and in children only if atypical (age less than 1 or >10, hypertension, haematuria, low complement, renal impairment) or steroid-resistant. Interpreted on light microscopy, immunofluorescence and electron microscopy — MCD (normal LM, foot-process effacement), membranous (subepithelial IgG4 deposits, spike-and-dome), FSGS (segmental sclerosis), amyloid (Congo-red positive). [1]

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SAQ 4 — Describe the management of minimal change disease in a child

• First-line: oral prednisolone 60 mg/m²/day (1 mg/kg/day) for 4-6 weeks, then an alternate-day taper over 4-6 weeks; ~90% achieve remission. No biopsy for a classic first presentation.
• Supportive: salt restriction, loop diuretic for oedema, ACE inhibitor/ARB to reduce proteinuria, pneumococcal/influenza vaccination, and consider anticoagulation if severely hypoalbuminaemic.
• Frequently-relapsing / steroid-dependent: low-dose alternate-day steroid, then a steroid-sparing agent — calcineurin inhibitor (ciclosporin/tacrolimus) or rituximab.
• Steroid-resistant (no remission by 4-6 weeks): biopsy (to exclude FSGS/genetic disease), calcineurin inhibitor or rituximab; higher risk of progression to ESKD. [1]

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SAQ 5 — Why are nephrotic patients prone to infection, and how is it prevented?

Mechanism: urinary loss of IgG and alternative-pathway complement factors B and D impairs opsonisation of encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae, E. coli). This causes spontaneous bacterial peritonitis, cellulitis, pneumonia and pneumococcal sepsis. [1]

Prevention and treatment: vaccinate — pneumococcal (conjugate and/or polysaccharide), annual influenza, and hepatitis B, ideally before immunosuppression (avoid live vaccines on immunosuppression); treat any suspected infection promptly with empirical broad-spectrum antibiotics without waiting for cultures. [1]

References

1. [1]Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases Kidney Int, 2021.PMID 34556256
2. [2]Fervenza FC, Appel GB, Barbour SJ, et al. Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy N Engl J Med, 2019.PMID 31269364
3. [3]Dahan K, Debiec H, Plaisier E, et al. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up J Am Soc Nephrol, 2017.PMID 27352623
4. [4]Beck LH Jr, Bonegio RGB, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy N Engl J Med, 2009.PMID 19571279
5. [5]Fernández-Juárez G, Rojas-Rivera J, van de Logt AE, et al. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy Kidney Int, 2021.PMID 33166580
6. [6]Iijima K, Sako M, Nozu K, et al. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial Lancet, 2014.PMID 24965823
7. [7]Llach F Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome Kidney Int, 1985.PMID 3906225
8. [8]Kerlin BA, Iorember FM, Callerame KL, et al. Exploring the Role of Antithrombin in Nephrotic Syndrome-Associated Hypercoagulopathy: A Multi-Cohort Study and Meta-Analysis Clin J Am Soc Nephrol, 2023.PMID 36754010
9. [9]Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease Kidney Int, 2024.PMID 38490803