Nephrotic Syndrome — Viva Questions

Rapid-fire examiner prompts with model answers. Each answer should be delivered in 30-60 seconds. [1]

Definition

Q. Define nephrotic syndrome. Tetrad: heavy proteinuria over 3.5 g/day (over 50 mg/kg/day), hypoalbuminaemia (albumin under 30 g/L), oedema, and hyperlipidaemia/lipiduria — from glomerular filtration-barrier (podocyte) injury. [1]

Q. Distinguish nephrotic from nephritic syndrome. Nephrotic = proteinuria-dominant (oedema, lipiduria, few cells in sediment); nephritic = haematuria, RBC casts, hypertension, renal impairment, oliguria, often low complement. [1]

Causes by age

Q. Commonest cause in a child? In an adult? Child — minimal change disease (steroid-responsive). Adult — membranous nephropathy and FSGS (primary); diabetic nephropathy is the commonest secondary cause. [1]

Q. Give the malignancy associations. Membranous nephropathy ↔ carcinoma (lung, colon, stomach, breast); minimal change disease ↔ Hodgkin lymphoma. [1]

Pathophysiology

Q. Where does the protein leak come from? Podocyte foot-process effacement destroys the charge/size selectivity of the glomerular filtration barrier. [1]

Q. Why is the nephrotic patient hypercoagulable? Urinary loss of antithrombin III, increased hepatic fibrinogen and factor VIII, platelet activation, and hemoconcentration/hyperviscosity. [1]

Q. Why hyperlipidaemia? The liver up-regulates lipoprotein synthesis in response to the low oncotic pressure / low albumin. [1]

Diagnosis

Q. How do you confirm nephrotic syndrome? Quantify proteinuria (24-h protein over 3.5 g/day, or UPCR over 300 mg/mmol); albumin under 30 g/L; lipiduria (oval fat bodies, Maltese cross under polarised light). [1]

Q. When do you biopsy? All adults. Children only if atypical (age less than 1 or >10, hypertension, haematuria, low complement, renal impairment) or steroid-resistant. [1]

Q. What antibody defines primary membranous nephropathy? Anti-PLA2R (M-type phospholipase A2 receptor) antibody, IgG4 subclass — ~70-80% of cases. [1]

Complications

Q. A nephrotic patient gets sudden flank pain and haematuria. Diagnosis? Renal vein thrombosis — image (Doppler/CT venography) and anticoagulate. [1]

Q. Why are nephrotic patients prone to infection? Loss of IgG and alternative-pathway complement (factor B and D) — encapsulated organisms; spontaneous bacterial peritonitis. [1]

Treatment

Q. First-line treatment for minimal change disease? Prednisolone 60 mg/m²/day (1 mg/kg/day) for 4-6 weeks, then alternate-day taper. [1]

Q. Which drug class reduces proteinuria in ALL causes? ACE inhibitor or ARB — lowers intraglomerular pressure; continue long-term. [1]

Q. When do you anticoagulate? When albumin is under 25-30 g/L (especially membranous nephropathy), or after any thrombotic event. [1]

Q. Evidence for rituximab in membranous? MENTOR trial — rituximab non-inferior to cyclosporine with a lower relapse rate. [1]

Pearls

Q. Frothy urine + periorbital oedema + Maltese cross in a 4-year-old? Minimal change disease — start prednisolone. [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