Chapter 18 · Proteinuria · Nephrotic Syndrome · Renal Hypertension

Normal values · Detection (dipstick, PCR, ACR) · Glomerular vs tubular proteinuria · Persistent asymptomatic proteinuria · Idiopathic nephrotic syndrome (MCNS, FSGS) · Syndromic & secondary NS · BP measurement · Hypertensive child assessment · Causes & treatment
📌 Core principles: Quantify proteinuria (PCR >200 mg/mmol = nephrotic range); MCNS most common in children; steroid sensitivity defines prognosis; treat hypertension with ACEi/ARB; lifestyle + pharmacotherapy.

📖 Proteinuria · Nephrotic Syndrome · Renal Hypertension

🔬 Proteinuria
Normal values: <150 mg/day or urine protein/creatinine ratio (PCR) <20 mg/mmol.
Detection: Dipstick (trace–1+ may be benign), PCR, albumin/creatinine ratio (ACR).
Intermittent: fever, exercise, orthostatic (common in adolescents).
Persistent: glomerular (albuminuria, hematuria, hypertension) or tubular (low-molecular-weight proteins, e.g. β2-microglobulin).
Persistent asymptomatic proteinuria – monitor, consider biopsy if heavy.
🧪 Nephrotic syndrome
Idiopathic (MCNS): minimal change disease (80%): edema, proteinuria >40 mg/m²/h or PCR >200 mg/mmol, hypoalbuminemia <25 g/L, hyperlipidemia. Steroid sensitive.
FSGS: steroid resistant, poor prognosis.
Familial & syndromic: NPHS1 (Finnish type), Denys-Drash, Pierson, Galloway-Mowat.
Secondary: Henoch–Schönlein, SLE, infections (HBV, malaria, HIV), drugs (NSAIDs).
❤️ Renal hypertension
BP measurement: appropriate cuff, age/sex/height percentile; confirm elevated readings.
Assessment: history (drugs, FH, birth weight), physical (radiofemoral delay, abdominal bruit), labs (U&E, renin, aldosterone, urinary catecholamines), renal Doppler, DMSA/MAG3.
Causes: renovascular (fibromuscular dysplasia, Takayasu), parenchymal (chronic pyelonephritis, reflux nephropathy, cystic disease), endocrine (coarctation, hyperaldosteronism).
Treatment: lifestyle, single drug (ACEi, CCB), escalate; BP goal <90th percentile or <130/80 in adolescents.

🔎 Symptom-based approach to proteinuria & nephrotic syndrome

1️⃣
Edema + frothy urine – Suspect nephrotic syndrome. Check urine dipstick (3-4+ protein), serum albumin, cholesterol, PCR.
2️⃣
Asymptomatic proteinuria on dipstick – Confirm first morning urine. Orthostatic proteinuria (normal supine, elevated upright) is benign. If persistent >1+ → PCR, assess renal function, consider referral.
3️⃣
Hypertension + proteinuria – Glomerulonephritis (PSGN, IgA, lupus). Check complement (C3), ANA, renal biopsy if progressive.
4️⃣
Steroid-resistant nephrotic syndrome – Consider FSGS, genetic causes (NPHS2), secondary biopsy, calcineurin inhibitors.
5️⃣
Low-molecular-weight proteinuria (β2-microglobulin, RBP) – Tubular proteinuria (interstitial nephritis, Fanconi syndrome, Wilson disease).
⚠️ Emergency signs in nephrotic syndrome: Spontaneous bacterial peritonitis (fever, abdominal pain), hypovolemic shock, thrombosis (limb swelling, tachypnea), anasarca with respiratory compromise.

📋 Management algorithms: Nephrotic syndrome & Hypertension

A
Idiopathic nephrotic syndrome (MCNS) – first episode
▪️ Admit if anasarca, severe edema, infection risk.
▪️ Prednisolone 60 mg/m²/day (max 80 mg) for 4-6 weeks, then taper over 2-3 months.
▪️ Salt restriction, diuretics for severe edema (furosemide, albumin infusion if hypovolemic).
▪️ Pneumococcal vaccine, varicella vaccine (if not immune).
▪️ Monitor for relapses – steroid sensitive relapses: short course prednisolone.
▪️ Frequent relapses or steroid dependent: consider steroid-sparing agents (levamisole, cyclophosphamide, calcineurin inhibitors).
B
Steroid-resistant nephrotic syndrome (SRNS)
▪️ Renal biopsy (FSGS most common). Genetic testing (NPHS1, NPHS2, WT1).
▪️ CNI (tacrolimus/cyclosporine) ± low-dose steroids.
▪️ Manage proteinuria with ACEi/ARB, control BP.
▪️ Prepare for renal replacement therapy if progressive.
C
Renal hypertension – stepwise treatment
▪️ Lifestyle: salt restriction (DASH diet), exercise, weight management.
▪️ First-line monotherapy: ACE inhibitor (lisinopril, enalapril) or ARB (candesartan) if proteinuria present; CCB (amlodipine) if not.
▪️ Add second agent if uncontrolled: amlodipine + ACEi or β-blocker (atenolol).
▪️ Treat underlying cause: angioplasty for renal artery stenosis, nephrectomy for non-functioning kidney (severe reflux nephropathy).
▪️ BP target: <90th percentile for age/height (or <130/80 in adolescents).

💡 Reflex prompts – Proteinuria · Nephrotic syndrome · Renal hypertension

🧪 A 4-year-old with periorbital edema, PCR 350 mg/mmol, albumin 1.8 g/dL. Most likely diagnosis?
Idiopathic nephrotic syndrome (minimal change disease). Start prednisolone.
📏 How to quantify proteinuria in children?
Spot urine protein/creatinine ratio (PCR) or albumin/creatinine ratio (ACR). PCR >200 mg/mmol = nephrotic range.
⚠️ A child on prednisolone for nephrotic syndrome develops fever, abdominal pain, and tenderness. What complication?
Spontaneous bacterial peritonitis (SBP). Urgent paracentesis and IV antibiotics (cefotaxime).
🩺 First-line treatment for a hypertensive child with proteinuric CKD?
ACE inhibitor (enalapril, lisinopril) – reduces proteinuria and BP, slows CKD progression.
📉 Orthostatic proteinuria: typical pattern?
Elevated protein only in upright position (after ambulation), negative after lying supine. Benign, resolves with age.
💊 Steroid-dependent nephrotic syndrome – next steroid-sparing agent?
Levamisole (good evidence), cyclophosphamide, mycophenolate mofetil, rituximab (for frequent relapses).
🩸 Which vaccine should be given before initiating high-dose steroids in nephrotic syndrome?
Pneumococcal conjugate vaccine (PCV13) and varicella vaccine if not previously infected/immunized.
🔍 Most common cause of secondary nephrotic syndrome in children worldwide?
Malaria (quartan malarial nephropathy, especially in Africa).
📊 A 14-year-old with BP 145/92 mmHg, BMI 31, no proteinuria. First step?
Lifestyle modification (weight loss, exercise, DASH diet) for 3-6 months; start pharmacotherapy if persists.
🧬 Genetic nephrotic syndrome Finnish type (CNF) – gene involved?
NPHS1 (nephrin) – congenital nephrotic syndrome, presents at birth.