Paediatrics chapters
Haematuria and acute post-streptococcal glomerulonephritis
How to approach red urine in a child, how glomerular and lower-tract bleeding differ, and the classic nephritic illness that follows a streptococcal throat or skin infection.
- Haematuria is more than about 5 red cells per high-power field in centrifuged urine; brown or cola urine, red cell casts and dysmorphic red cells mean a glomerular source, bright red urine with normal cells a lower tract source.
- PSGN follows group A streptococcal throat infection by 1 to 2 weeks or skin infection by 3 to 6 weeks, with cola urine, periorbital oedema, hypertension and oliguria, and a low C3 that normalises in 6 to 8 weeks.
- Treatment is supportive (salt and fluid restriction, furosemide, antihypertensives, penicillin for carriage); over 95% recover fully.
On this page
Overview
Red urine worries parents and doctors alike. Some red urine is not blood at all; some blood comes from a harmless source; and some signals glomerulonephritis (GN). Acute post-streptococcal glomerulonephritis (PSGN) is the commonest form of acute GN and the commonest immune-mediated nephritis in children. It is a self-limiting illness, but in the acute phase hypertension, fluid overload and AKI can be dangerous.
Haematuria
Definition
- Microscopic haematuria: more than 5 red cells per high-power field in a centrifuged, freshly voided midstream sample (Akbar; Nelson gives more than 3 to 5). Seen only on dipstick or microscopy.
- Gross (macroscopic) haematuria: visible; urine may be pink, red, brown or smoky.
- Two or more consecutive positive samples make it more meaningful. Isolated microscopic haematuria is found in up to about 4% of healthy children and is often transient.
Red urine that is not haematuria
| Dipstick | Microscopy | Think of |
|---|---|---|
| Negative | No red cells | Foods and dyes (e.g. beetroot), drugs (rifampicin, desferrioxamine), urate crystals in infants |
| Positive | No red cells | Haemoglobinuria (intravascular haemolysis, e.g. malaria) or myoglobinuria (rhabdomyolysis) |
| Positive | Red cells present | True haematuria |
The dipstick reacts with haemoglobin and myoglobin, not only with intact red cells. Always confirm red cells by microscopy.
Causes
| Site | Causes |
|---|---|
| Glomerular | PSGN and other post-infectious GN, IgA nephropathy, MPGN, rapidly progressive GN, Henoch-Schönlein purpura, SLE, HUS, Alport syndrome, thin basement membrane disease |
| Tubulointerstitial / renal | Pyelonephritis, interstitial nephritis, polycystic kidneys, Wilms tumour, renal vein thrombosis, sickle cell trait or disease, trauma |
| Lower tract | UTI (cystitis, urethritis), stones, hypercalciuria, trauma, cyclophosphamide cystitis |
| Other | Bleeding disorders, low platelets, anticoagulants, strenuous exercise, menstrual contamination |
PSGN is the commonest acute GN; IgA nephropathy is the commonest chronic GN in children. The commonest lower-tract causes are UTI, stones and hypercalciuria.
Glomerular versus lower-tract bleeding
| Feature | Glomerular | Non-glomerular (lower tract) |
|---|---|---|
| Colour | Brown, tea or cola | Bright red, may have clots |
| Red cell shape | Dysmorphic (distorted, small, fragmented) | Normal |
| Red cell casts | Present | Absent |
| Proteinuria | Often more than 1+ | Little |
| Timing in stream | Throughout | Start or end of stream |
| Associated | Oedema, hypertension, oliguria | Dysuria, colic, frequency |
"Casts come from the kidney": red cell casts are moulded in tubules, so they prove a renal source.
Clinical clues
- Painful haematuria: dysuria (cystitis), loin pain (pyelonephritis), colicky radiating pain (stone), trauma.
- Painless gross haematuria: sickle cell trait, Wilms tumour, exercise, IgA nephropathy.
- Haematuria during an upper respiratory infection: IgA nephropathy; haematuria 1 to 3 weeks after a sore throat: PSGN.
- Deafness and family history of kidney failure: Alport syndrome; relatives with harmless haematuria: thin basement membrane disease.
- Rash, joint pain, abdominal pain: HSP; malar rash, arthritis: SLE.
- Bloody diarrhoea, pallor, petechiae: HUS.
Evaluation
- Confirm red cells on microscopy; look for casts and red cell shape.
- Isolated asymptomatic microscopic haematuria: repeat urinalysis (at least twice, a week or more apart); if it persists, check urine calcium:creatinine ratio, test relatives' urine, sickle screen, renal function and ultrasound.
- Gross or symptomatic haematuria: urine culture, urine protein:creatinine, urine calcium:creatinine (hypercalciuria), urea, creatinine, electrolytes, albumin, C3 and C4, ASO titre, throat swab, ANA and anti-dsDNA, full blood count (platelets for HUS and HSP), clotting screen.
- Ultrasound: for gross haematuria, suspected anomalies, stones, and to exclude Wilms tumour in children under 5.
- MCUG if reflux is suspected; renal biopsy in selected cases (persistent nephritis, heavy proteinuria, falling function).
A low C3 narrows glomerular haematuria to PSGN, MPGN or lupus nephritis.
Acute post-streptococcal glomerulonephritis
Aetiology and epidemiology
- Follows infection with a nephritogenic strain of group A beta-haemolytic streptococcus, of the throat or the skin (impetigo, pyoderma); occasionally after otitis media or scarlet fever.
- About 10 to 15% of children infected with a nephritogenic strain develop nephritis; cases cluster in families, but second attacks are rare (type-specific immunity).
- Peak age 5 to 10 years; rare under 3 years.
| Feature | After pharyngitis | After pyoderma |
|---|---|---|
| Climate and season | Temperate; winter and spring | Hot, tropical; summer and autumn |
| Age | School age (5 to 10 years) | Preschool (under 5) |
| Latent period | 1 to 2 weeks | 3 to 4 weeks (Nelson: 4 to 6) |
| Sex | Boys 2:1 | Equal |
| Best antibody | ASO | Anti-DNase B |
"Throat is quick, skin is slow": about 10 days after a sore throat, about a month after impetigo.
Pathogenesis
- An immune-complex disease: streptococcal antigen-antibody complexes form in the blood or in situ, lodge in the glomeruli and activate complement (hence the low C3).
- Both kidneys and almost all glomeruli are affected. Kidneys are swollen with tiny cortical bleeds.
- Light microscopy: swollen endothelial cells, proliferation of mesangial cells and neutrophil infiltration (diffuse proliferative GN); crescents in severe cases.
- Electron microscopy: deposits on the epithelial (outer) side of the basement membrane (subepithelial humps).
- Immunofluorescence: granular deposits.
Clinical features
- Abrupt onset with headache, malaise and vomiting; the throat or skin infection has usually healed.
- Haematuria: cola-coloured or smoky urine in about 30 to 50%; microscopic in the rest.
- Oedema: periorbital puffiness in most (about 85%), worse in the morning; gross oedema is unusual.
- Oliguria, flank or abdominal pain.
- Hypertension in about 70%: headache, vomiting, confusion, visual upset, seizures (hypertensive encephalopathy in about 5%).
- Circulatory overload: breathlessness, heart failure, pulmonary oedema.
- AKI in a proportion.
The acute nephritic picture is haematuria, oedema, hypertension and oliguria with mild proteinuria, in contrast to nephrotic syndrome (heavy proteinuria, low albumin, normal BP).
Investigations
| Test | Finding |
|---|---|
| Urinalysis | Gross or microscopic haematuria, dysmorphic red cells and red cell casts, some white cells; mild proteinuria; high specific gravity |
| Urea and creatinine | Raised; hyponatraemia (dilutional) and hyperkalaemia |
| Blood count, ESR | ESR raised; haemoglobin low from haemodilution; white count usually normal |
| Serum C3 | Low in over 95%; returns to normal in 6 to 8 weeks |
| ASO titre | Raised (over 200 units/mL) in 80 to 90% after pharyngitis, less often after skin infection |
| Anti-DNase B | Best marker after skin infection; streptozyme test detects several antibodies |
| Throat swab culture | May grow streptococci but about 20% of children are healthy carriers, so it does not prove the diagnosis |
| Chest X-ray | Cardiomegaly, perihilar congestion from fluid overload |
| Renal biopsy | Rarely needed: consider for AKI that does not settle, nephrotic-range proteinuria, or low C3 persisting beyond 8 weeks |
A C3 that stays low after 8 weeks is not PSGN; think of membranoproliferative GN and biopsy.
Management
All treatment is supportive; the disease settles by itself.
- Admit for monitoring of blood pressure, weight, input-output and renal function; bed rest in the acute phase.
- Antibiotic: penicillin to clear remaining streptococci and stop spread of the nephritogenic strain (Akbar: benzyl penicillin 500,000 units IM twice daily, or oral penicillin V 250 mg four times daily, for 5 to 7 days). It does not alter the course of the nephritis.
- Salt and fluid restriction: fluid limited to insensible loss (about 400 to 500 mL/m²/day) plus urine output when oliguric; sodium limited (Akbar: about 1 to 2 g/day); avoid potassium-rich foods such as fruit juice.
- Diuretic: furosemide for oedema and overload.
- Hypertension: furosemide plus a calcium channel blocker (amlodipine or nifedipine) or beta-blocker; IV hydralazine or other parenteral drugs for hypertensive encephalopathy. ACE inhibitors and ARBs are avoided while AKI is present.
- Pulmonary oedema: sit up, oxygen, furosemide, salt and fluid restriction.
- Hyperkalaemia and acidosis: treat as in AKI.
- Dialysis if anuria persists beyond 2 to 3 days, or for refractory overload, potassium or acidosis.
Unlike rheumatic fever, early antibiotic treatment of the sore throat does not prevent PSGN, and long-term penicillin prophylaxis is not needed because second attacks are rare.
Complications
- Hypertensive encephalopathy (headache, vomiting, seizures, visual loss).
- Heart failure and pulmonary oedema from fluid overload.
- Acute kidney injury, hyperkalaemia, acidosis.
- Rarely, rapidly progressive (crescentic) GN.
Course and prognosis
| Feature | Usual course |
|---|---|
| Oliguria, oedema, hypertension | Settle within about 1 to 2 weeks (acute phase 4 to 10 days; hypertension gone by 3 weeks) |
| Gross haematuria | Seldom beyond 2 weeks |
| C3 | Normal by 6 to 8 weeks |
| Proteinuria | Low-grade, may last up to 6 months |
| Microscopic haematuria | May last 1 to 2 years |
- Over 95% recover completely; fewer than 1% develop CKD; a small number die in the acute phase.
- Long-term follow-up of urine and blood pressure is sensible.
Differential diagnosis of acute nephritis
| Condition | Distinguishing points |
|---|---|
| IgA nephropathy (Berger disease) | Gross haematuria within 1 to 2 days of an upper respiratory or gut infection; recurrent; boys; normal C3; IgA deposits in the mesangium on biopsy; the commonest chronic GN; progresses in some over many years |
| MPGN | Persistently low C3; nephritic-nephrotic picture; tends to progress |
| Lupus nephritis | Adolescent girls; rash, arthritis; low C3 and C4, ANA and anti-dsDNA positive |
| HSP nephritis | Palpable purpura on legs and buttocks, arthritis, abdominal pain; normal platelets and normal C3; IgA deposits |
| Alport syndrome | Usually X-linked, type IV collagen defect; haematuria with sensorineural deafness; boys progress to kidney failure |
| Thin basement membrane disease | Benign familial haematuria; often autosomal dominant; does not progress |
| HUS | Bloody diarrhoea, haemolytic anaemia with fragmented cells, low platelets |
| Rapidly progressive GN | Rapidly rising creatinine; crescents on biopsy; needs urgent treatment |
Low C3 club: "PSGN, MPGN, Lupus". Normal C3: IgA, HSP, Alport, thin membrane.
Expect: definition of microscopic haematuria; red urine without red cells (haemoglobin, myoglobin, rifampicin, urates); features of glomerular bleeding (cola urine, red cell casts, dysmorphic cells); PSGN after group A streptococcal throat (1 to 2 weeks) or skin (3 to 6 weeks) infection in a 5 to 10 year old; cola urine, periorbital oedema, hypertension and oliguria; low C3 recovering by 6 to 8 weeks and MPGN if it does not; ASO after pharyngitis and anti-DNase B after skin infection; supportive treatment with penicillin, salt and fluid restriction, furosemide and antihypertensives; antibiotics not preventing PSGN; hypertensive encephalopathy as a key complication; excellent prognosis; and IgA nephropathy with synpharyngitic haematuria and normal C3.
Quick revision
- Microscopic haematuria: over 5 red cells per high-power field; confirm by microscopy.
- Dipstick positive, no red cells: haemoglobin or myoglobin.
- Glomerular: cola urine, red cell casts, dysmorphic cells, proteinuria.
- PSGN: group A strep; throat 1 to 2 weeks, skin 3 to 6 weeks; age 5 to 10.
- Immune complexes, low C3, subepithelial humps, granular immunofluorescence.
- Cola urine, periorbital oedema, hypertension (encephalopathy), oliguria, overload.
- C3 normal by 8 weeks, else MPGN; ASO (throat), anti-DNase B (skin).
- Supportive: penicillin, salt and fluid restriction, furosemide, calcium channel blocker; dialysis if anuric.
- Over 95% full recovery; microscopic haematuria may last 1 to 2 years.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
Why is C3 low in post-streptococcal glomerulonephritis?
Immune complexes deposited in the glomeruli activate complement, consuming C3. It returns to normal within 6 to 8 weeks; if it does not, another lesion such as MPGN is likely.
Does giving penicillin for a sore throat prevent PSGN?
No. Treating the streptococcal infection does not prevent nephritis, although penicillin is still given to clear the organism and stop it spreading.
How is IgA nephropathy different from PSGN?
In IgA nephropathy visible haematuria appears within a day or two of a respiratory infection, tends to recur and C3 is normal; in PSGN there is a latent period of one to several weeks and C3 is low.
What is the most dangerous early complication of PSGN?
Severe hypertension with encephalopathy (headache, vomiting, seizures) and fluid overload causing heart failure or pulmonary oedema.