Preparatory Mindset
Nephrotic syndrome and urinary tract infection are "glomerular vs tubular" topics. Nephrotic syndrome is defined by the tetrad — proteinuria >3.5 g/day, hypoalbuminaemia, oedema, hyperlipidaemia — and the exam skill is matching the histology to the clinical picture: minimal change disease (MCD — children, steroid-responsive), membranous nephropathy (MN — adults, 40%, anti-PLA2R, thromboembolism), focal segmental glomerulosclerosis (FSGS — adults, HIV/heroin, steroid-resistant), membranoproliferative GN (MPGN), with diabetic nephropathy and lupus nephritis as the classic secondary causes. The complications are the high-yield part: thromboembolism (renal vein thrombosis up to 40%), infections, AKI, dyslipidaemia. UTI is pattern-recognition: lower (cystitis) vs upper (pyelonephritis), uncomplicated vs complicated, with the HKHA empiric regimens (amoxicillin-clavulanate / nitrofurantoin for cystitis; IV agents for pyelonephritis) and the "don't treat asymptomatic bacteriuria" rule as LMCHK must-knows.
Core Concepts
Nephrotic syndrome — definition (updated 2024)
- Proteinuria >3.5 g/day (adults) (or spot protein:creatinine >3.5 g/g); children — >40 mg/m²/h or >50 mg/kg/day. - Hypoalbuminaemia <30 g/L; oedema (periorbital, dependent, ascites, anasarca); hyperlipidaemia ± lipiduria (oval fat bodies, fatty casts). - "Nephrotic-range proteinuria" alone is not the syndrome — the full tetrad is required.
- Nephrotic syndrome = heavy proteinuria + hypoalbuminaemia + oedema + hyperlipidaemia:
Aetiology (primary glomerular disease ~75%)
| Primary glomerulopathy | Frequency | Key features |
|---|---|---|
| Minimal change disease (MCD) | 15% (children ~most common) | Normal LM, podocyte foot-process effacement on EM; ~90% of children and ~50% of adults respond to prednisone |
| Membranous nephropathy (MN) | 40% (most common in adults) | Thickened GBM (immune deposits); anti-PLA2R antibody; spontaneous remission or progressive; thromboembolism risk |
| Focal segmental glomerulosclerosis (FSGS) | 15% | Segmental sclerosis; primary or secondary (HIV, heroin, obesity, reflux); steroid-resistant, progresses to ESRD |
| Membranoproliferative GN (MPGN) | 7% | Mesangial + subendothelial deposits, "tram-track"; hypocomplementaemia; HCV (cryoglobulinaemia) |
| Mesangioproliferative GN (MsPGN) | 5% | IgA nephropathy etc. |
Secondary causes (~25%): diabetic nephropathy (most common secondary; albuminuria + declining GFR), lupus nephritis (class I–VI; class IV diffuse proliferative — most severe, immunosuppression), amyloidosis, myeloma (light-chain), infection (HBV/HCV, HIV), drugs (NSAIDs, gold, penicillamine), malignancy (paraneoplastic — MN with lung/GI cancer), pre-eclampsia.
Pathophysiology
- Glomerular basement membrane/podocyte damage → massive proteinuria → hypoalbuminaemia → ↓ oncotic pressure → oedema; hepatic lipoprotein synthesis ↑ → hyperlipidaemia; loss of anticoagulant proteins (antithrombin III, protein C/S) + hyperviscosity + platelet activation → hypercoagulability (thromboembolism); loss of immunoglobulins/complement → infection risk; hypovolaemia → pre-renal AKI; vitamin D/thyroid-binding protein loss.
Clinical features & complications
- Thromboembolism: renal vein thrombosis (up to 40% in MN), DVT, pulmonary embolism, arterial thrombosis — anticoagulate (LMWH/warfarin) in high-risk MN; spontaneous peripheral arterial/venous thrombosis. - Infection: pneumococcal peritonitis, cellulitis (loss of IgG/complement) — treat promptly. - AKI: hypovolaemia, diuretic overuse, acute tubular injury. - Dyslipidaemia, malnutrition, hypothyroidism, anaemia.
- Oedema (periorbital in the morning, ankle oedema, ascites, pleural effusions, genital oedema); frothy urine.
- Complications (exam favourites):
- Clinical case classic: nephrotic child (MCD) — periorbital oedema, proteinuria, responds to steroids; adult with MN + unilateral flank pain + haematuria → renal vein thrombosis.
Diagnosis
- Urine: 24-h protein >3.5 g (or protein:Cr ratio), lipiduria (oval fat bodies); FBC, albumin, lipids, renal function; anti-PLA2R (MN), ANA/anti-dsDNA (lupus), complement (MPGN/lupus), HBsAg/HCV/HIV, serum/urine electrophoresis + free light chains (myeloma/amyloid), renal biopsy for definitive diagnosis (light microscopy, immunofluorescence, EM).
- Decreased renal function present in 25–50% at diagnosis (MN/FSGS); microscopic haematuria ~30%.
Treatment
- MCD: prednisone (90% children/50% adults respond); steroid-dependent/frequent-relapse → cyclophosphamide/calcineurin inhibitor/rituximab. - MN: conservative first (ACEi/ARB + anticoagulation); moderate–high risk → rituximab, cyclophosphamide ± steroids, calcineurin inhibitors. - FSGS: steroids (less responsive), calcineurin inhibitors; control secondary causes (HIV — ART; obesity). - MPGN: treat cause (HCV — antivirals); steroids if idiopathic. - Lupus nephritis (class III/IV): high-dose steroids + cyclophosphamide or mycophenolate (MMF). - Diabetic nephropathy: glycaemic control, ACEi/ARB, SGLT2i, BP control.
- General: dietary salt restriction, diuretics (frusemide; HCTZ 2 mg/kg/day, spironolactone 2–4 mg/kg/day in children; dextran for refractory), ACEi/ARB (reduce proteinuria + BP), statins (hyperlipidaemia), anticoagulation for thromboembolism/very low albumin in MN, treat infections, albumin infusion in severe hypoalbuminaemia (with diuretic).
- Immunosuppression:
- Renal biopsy indications: adults (histology changes management), steroid-resistant, rapid decline, suspected secondary cause.
Urinary tract infection (UTI)
- Uncomplicated cystitis: analgesics + fluids; empirical 7-day oral — amoxicillin-clavulanate or nitrofurantoin (avoid if CrCl <30 mL/min); fluoroquinolones generally avoided for uncomplicated cystitis (FDA warning). - Acute pyelonephritis: prompt effective empirical IV antibiotics — amoxicillin-clavulanate, or piperacillin-tazobactam if Pseudomonas suspected, or meropenem for severe/deteriorating; complete 14-day course; switch to oral when improving (guided by cultures). - Complicated UTI: treat underlying urological abnormality, broader cover, longer course; catheter — consider removal/replacement. - Asymptomatic bacteriuria: do NOT treat except in pregnancy and patients undergoing invasive urological procedures (no clinical benefit).
- Definition: infection of the urinary tract — lower (cystitis: bladder), upper (pyelonephritis: kidney ± ureters); uncomplicated (healthy non-pregnant women) vs complicated (structural/functional abnormality, catheter, male, pregnancy, renal impairment, immunosuppression).
- Epidemiology: very common — women >> men; catheter-associated UTIs the most common nosocomial infection.
- Pathogens: E. coli (most common), Klebsiella, Proteus, Enterococcus, Group B strep, S. saprophyticus (young women); Pseudomonas (catheter/complicated); S. aureus (haematogenous).
- Lower UTI (cystitis): dysuria, frequency, urgency, suprapubic pain, cloudy/haematuric urine; no fever/loin pain.
- Upper UTI (pyelonephritis): fever, chills, loin pain/CVA tenderness, nausea/vomiting; may progress to sepsis/bacteraemia; complicated by abscess, obstruction, papillary necrosis (diabetes, NSAIDs), emphysematous pyelonephritis.
- Diagnosis: urine dipstick (nitrites, leukocyte esterase) + MSU microscopy (pyuria, bacteriuria, WBC casts in pyelonephritis) + culture & sensitivity; blood cultures if febrile/severe; imaging (CT/USG) if complicated, recurrent, stones suspected, or obstruction.
- Treatment:
- Complications: bacteraemia/sepsis, perinephric abscess, emphysematous pyelonephritis, papillary necrosis, recurrent UTI, renal scarring (children).
HKHA Handbook (LMCHK) — Key Points
- Uncomplicated cystitis: analgesics + oral fluids; empirical therapy (generally 7 days): amoxicillin-clavulanate or nitrofurantoin (avoid if CrCl <30 mL/min); FDA warns against fluoroquinolones for uncomplicated cystitis unless no alternative. - Acute pyelonephritis: analgesics/antipyretics, fluid resuscitation ± inotropes for severe; prompt effective IV antibiotics — amoxicillin-clavulanate, or piperacillin-tazobactam (if Pseudomonas), or meropenem (severe/deteriorating); review on culture results; complete 14-day course. - Asymptomatic bacteriuria: treatment NOT recommended except in pregnancy and patients undergoing invasive urological procedures.
- UTI (In 9):
- Renal failure (K 22–24) — AKI/CKD management applies to nephrotic complications (see AKI chapter).
- LMCHK message: nephrotic syndrome → always check for secondary causes (diabetes, lupus, HBV/HCV, malignancy, amyloid); MN → anti-PLA2R + anticoagulation for thromboembolism; MCD in children → steroids first.
High-Yield Points
- Nephrotic tetrad: proteinuria >3.5 g/day + hypoalbuminaemia + oedema + hyperlipidaemia.
- MCD = children, steroid-responsive (90%); MN = adults (~40%), anti-PLA2R, thromboembolism (renal vein thrombosis up to 40%); FSGS = steroid-resistant, HIV/heroin; MPGN = tram-track, hypocomplementaemia, HCV.
- Secondary: diabetic nephropathy (most common), lupus nephritis, amyloid, myeloma.
- Complications: thromboembolism, infection, AKI, dyslipidaemia.
- UTI: E. coli most common; S. saprophyticus in young women; pyelonephritis → 14 days IV→oral.
- Cystitis: amoxicillin-clavulanate / nitrofurantoin (not if CrCl <30); avoid FQ for uncomplicated cystitis.
- Asymptomatic bacteriuria: treat only pregnancy + pre-urological procedure.
- Complicated UTI: structural abnormality → broader cover + imaging.
Topic Summary
Nephrotic syndrome is the tetrad of heavy proteinuria (>3.5 g/day), hypoalbuminaemia, oedema and hyperlipidaemia, caused by primary glomerulopathies (MCD in children — steroid-responsive; membranous nephropathy in adults — anti-PLA2R, thromboembolic; FSGS — steroid-resistant; MPGN) or secondary diseases (diabetic nephropathy, lupus nephritis, amyloid, myeloma). Management combines salt restriction, diuretics, ACEi/ARB, statins and disease-specific immunosuppression, with aggressive prevention of the four complications — thromboembolism, infection, AKI, dyslipidaemia. UTI spans cystitis (7-day amoxicillin-clavulanate/nitrofurantoin) to pyelonephritis (14-day IV regimen), with the HKHA rules — no fluoroquinolones for simple cystitis, treat asymptomatic bacteriuria only in pregnancy/procedures — as LMCHK priorities.