Nephrotic syndrome in Adults

💧🩺 Nephrotic syndrome in adults is defined by nephrotic-range proteinuria (typically >3.5 g/day, or urine PCR ≈ ≥300 mg/mmol), leading to hypoalbuminaemia, oedema, and a pro-thrombotic, infection-prone state. Key exam trap: despite dramatic oedema, the effective arterial blood volume may be low (secondary RAAS activation), so aggressive diuresis can precipitate AKI.

🧠 Pathophysiology (why these features happen)

• 🧱 Glomerular barrier injury → albumin leaks into urine → ↓ plasma oncotic pressure → fluid shifts into interstitium → oedema.
• 🧬 Compensatory liver response → ↑ lipoprotein synthesis → hypercholesterolaemia/hypertriglyceridaemia.
• 🩸 Hypercoagulability → urinary loss of anticoagulant proteins (e.g., antithrombin) + ↑ fibrinogen/platelet activation → ↑ VTE risk (renal vein thrombosis is the classic association).
• 🦠 Infection risk → urinary loss of IgG + oedema-related skin breakdown → cellulitis/peritonitis risk (esp. if immunosuppressed).

✅ Core diagnostic features

• 🧪 Proteinuria: nephrotic-range (classically >3.5 g/day, or urine PCR ≈ ≥300 mg/mmol).
• ⬇️ Hypoalbuminaemia: often <30 g/L (more severe hypoalbuminaemia increases VTE risk).
• 🌊 Oedema: periorbital (AM), dependent oedema, ascites/pleural effusions in severe cases.
• 📈 Hyperlipidaemia: can be marked (not diagnostic on its own).

🚩 Red flags (admit / urgent senior + nephrology)

• 🚨 Suspected VTE: pleuritic chest pain, dyspnoea, unilateral leg swelling, flank pain + haematuria (renal vein thrombosis).
• 🧯 Sepsis or rapidly progressive cellulitis.
• ⚡ AKI, hyperkalaemia, severe hypertension, or pulmonary oedema.
• 🧠 New confusion/seizures (think severe uraemia, severe electrolyte disturbance, hypertensive emergency).

📊 Causes (adult-friendly UK framing)

🔬 Investigations (what to send on day 1)

• 🧪 Quantify protein: urine PCR/ACR (don’t rely on dip alone).
• 🩸 Baseline bloods: U&E/eGFR, albumin, LFTs, lipids, FBC.
• 🧫 Urine: microscopy for haematuria/casts (helps spot nephritic overlap).
• 🧬 Cause screen (typical adult set): ANA, dsDNA, C3/C4, ANCA; HBV/HCV/HIV; HbA1c; serum electrophoresis + serum free light chains (± urine Bence Jones).
• 🩻 Imaging: renal ultrasound (size/obstruction); CXR if malignancy/systemic disease suspected.
• 🧾 Renal biopsy: generally essential in adults unless a very clear alternative explanation (e.g., typical longstanding diabetic nephropathy with retinopathy and no “atypical” features).

💊 Management principles (UK ward/clinic logic)

• 🎯 1) Treat the cause (usually nephrology-led): immunosuppression choices depend on histology + risk stratification.
• 🧂 2) Control oedema safely: salt restriction + loop diuretic (often higher doses needed); add a thiazide-like agent (e.g., metolazone) for synergy if resistant, with close U&E monitoring.
• 🚱 3) Avoid iatrogenic AKI: daily weights, strict I&O, check postural BP; if dizzy/oliguric with rising creatinine, you may be over-diuresing.
• 🧯 4) Reduce proteinuria: ACEi/ARB (as tolerated) lowers intraglomerular pressure and protein leak (watch creatinine/K+).
• 🫀 5) Cardiovascular risk: statin based on overall CV risk; nephrotic hyperlipidaemia can be dramatic but improves as proteinuria resolves.

🩸 Thrombosis prevention (important nuance)

• 🧠 Adults with nephrotic syndrome are at increased VTE risk; risk rises with very low serum albumin and certain diagnoses (notably membranous nephropathy). :contentReference[oaicite:0]{index=0}
• ⚖️ Prophylactic anticoagulation is not automatic: it’s an individualised risk–benefit decision (VTE risk vs bleeding risk), typically made with nephrology-especially when albumin is very low (e.g., ~<20–25 g/L) and additional risk factors are present. :contentReference[oaicite:1]{index=1}
• ✅ If VTE is suspected/confirmed: investigate and treat promptly (standard therapeutic anticoagulation, adjust for renal function and bleeding risk).

⚠️ Complications (and what to look for)

• 🩸 VTE: DVT/PE, renal vein thrombosis.
• 🦠 Infection: cellulitis, sepsis; higher risk if immunosuppressed.
• ⚡ AKI: from over-diuresis, renal vein thrombosis, intercurrent illness, nephrotoxins (NSAIDs!).
• 🦴 Bone/mineral issues: low total calcium due to low albumin; vitamin D binding protein loss can contribute to deficiency.

💡 Exam/ward pearls

• 🫧 “Frothy urine + oedema” = quantify protein (PCR/ACR) and check albumin-don’t guess.
• 🩺 Adults usually need a biopsy to direct therapy; avoid empiric steroids unless guided by nephrology.
• 🚨 Flank pain + haematuria + AKI in nephrotic syndrome = think renal vein thrombosis until proven otherwise.
• 💊 Avoid NSAIDs: they can both cause and worsen nephrotic syndrome and precipitate AKI.

📚 References

• KDIGO. Glomerular Disease Guideline – Key Takeaways (includes nephrotic syndrome definitions and thrombosis/anticoagulation considerations). :contentReference[oaicite:2]{index=2}
• NICE. Empagliflozin for treating chronic kidney disease (Technology appraisal). :contentReference[oaicite:3]{index=3}
• NICE. Dapagliflozin for treating chronic kidney disease (Technology appraisal / review document). :contentReference[oaicite:4]{index=4}
• UK Kidney Association. SGLT2 inhibitor guideline in CKD (UK practice recommendations). :contentReference[oaicite:5]{index=5}