Nephrotic syndrome in Adults
Related Subjects:
| Metabolic Acidosis
| Lactic Acidosis
| Acute Kidney Injury (AKI)
| Renal Physiology
| Chronic Kidney Disease (CKD)
| Anaemia in CKD
| Analgesic Nephropathy
| Medullary Sponge Kidney
| IgA Nephropathy (Berger's Disease)
| HIV-associated Nephropathy (HIVAN)
| Balkan Endemic Nephropathy (BEN)
| Autosomal Dominant Polycystic Kidney Disease
💧🩺 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)
| Primary (glomerular) |
Key associations / clues |
| 🧩 Membranous nephropathy |
Common adult cause; consider autoantibodies (e.g., PLA2R), malignancy screen depending on age/risk. |
| 🧱 FSGS |
Obesity, reduced nephron mass, HIV, heroin; often hypertension + reduced eGFR. |
| 🫧 Minimal change disease |
Less common in adults; NSAIDs, Hodgkin lymphoma; dramatic steroid response. |
| 🧬 MPGN / C3 glomerulopathy (less common) |
Complement pathway disease; may overlap nephritic features. |
| Secondary |
Examples |
| 🍬 Metabolic |
Diabetes mellitus (commonest secondary cause in UK practice). |
| 🧠 Autoimmune |
SLE (lupus nephritis), vasculitis (often nephritic overlap). |
| 🧡 Protein deposition |
Amyloidosis; light chain disease / myeloma. |
| 🦠 Infection-related |
HBV, HCV, HIV (plus others depending on global exposure history). |
| 💊 Drug-induced |
NSAIDs, lithium, interferons, bisphosphonates (e.g., pamidronate), others. |
| 🎗️ Malignancy-associated |
Solid tumours (esp. older adults), lymphoma (incl. Hodgkin with minimal change). |
🔬 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).
- ⚖️ 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.
- ✅ 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).
- NICE. Empagliflozin for treating chronic kidney disease (Technology appraisal).
- NICE. Dapagliflozin for treating chronic kidney disease (Technology appraisal / review document).
- UK Kidney Association. SGLT2 inhibitor guideline in CKD (UK practice recommendations).
