Medicine chapters
Nephritic versus nephrotic syndrome
How to tell the two main glomerular syndromes apart at the bedside and in the lab: blood and red cell casts with hypertension in nephritic syndrome, versus heavy proteinuria, low albumin, oedema and high lipids in nephrotic syndrome.
- Nephritic syndrome = glomerular inflammation: haematuria with red cell casts, hypertension, oliguria, mild oedema, rising creatinine and sub-nephrotic proteinuria.
- Nephrotic syndrome = leaky podocytes: proteinuria >3.5 g/day, low albumin, marked oedema and high lipids (fatty casts), usually with little blood.
- Low complement narrows a nephritic picture to post-infectious GN, lupus, MPGN, cryoglobulinaemia or endocarditis.
On this page
Overview
Glomerular diseases present in a few recognisable patterns. The two most important are:
- Nephritic syndrome: the glomeruli are inflamed (endothelial and mesangial cells). Red cells leak, GFR falls, salt and water are retained.
- Nephrotic syndrome: the podocyte filter is leaky. Large amounts of protein pass into the urine, but inflammation is slight.
Other glomerular patterns are rapidly progressive GN (nephritic syndrome with kidney failure over weeks), asymptomatic haematuria or proteinuria, and mixed pictures. Each pattern has its own list of causes, so naming the syndrome is the first step to the diagnosis.
Nephritic syndrome
Clinical presentation
- Haematuria: macroscopic ("smoky" or cola-coloured urine) or microscopic.
- Hypertension (salt and water retention).
- Oedema: mild, often periorbital, also legs or sacrum.
- Oliguria and a rising urea and creatinine (uraemia).
- Proteinuria, usually below the nephrotic range.
- Sometimes breathlessness from fluid overload or hypertensive encephalopathy.
PHAROH: Proteinuria (mild), Haematuria, Azotaemia, Red cell casts, Oliguria, Hypertension.
Main causes
- Post-streptococcal GN (children; 1–3 weeks after throat or skin infection).
- Other post-infectious GN: staphylococci, infective endocarditis, infected ventriculoatrial shunts, hepatitis B and C, visceral abscess.
- IgA nephropathy and IgA vasculitis (Henoch–Schönlein purpura).
- Lupus nephritis.
- Anti-GBM disease (Goodpasture), ANCA vasculitis (GPA, MPA): usually as RPGN.
- Membranoproliferative GN, cryoglobulinaemia.
- Alport syndrome (hereditary).
Nephrotic syndrome
Clinical presentation
- Oedema, often marked and generalised: periorbital in the morning (especially in children), legs, sacrum, genitals; may progress to ascites and pleural effusions (anasarca).
- Frothy urine.
- BP often normal at first; urine output and creatinine often normal early.
- Tiredness, breathlessness from effusions.
- Signs of complications: venous thrombosis (DVT, renal vein thrombosis), infections, xanthelasma.
Definition
Nephrotic syndrome needs proteinuria above 3.5 g a day with low albumin and oedema; hyperlipidaemia completes the classic tetrad.
Nephrotic syndrome is the combination of:
- Proteinuria >3.5 g/24 h in adults.
- Hypoalbuminaemia.
- Oedema.
- Hyperlipidaemia (and lipiduria).
Main causes
- Minimal change disease (commonest in children).
- Focal segmental glomerulosclerosis (commonest in people of African descent; HIV, heroin, obesity).
- Membranous nephropathy (classic primary cause in adults; hepatitis B, cancer, drugs).
- Diabetic nephropathy and amyloidosis (main secondary causes in adults).
- Lupus (class V), drugs (NSAIDs, penicillamine, gold), infections (malaria, hepatitis B and C, HIV).
Details are in the chapter on nephrotic syndrome in adults.
Distinguishing features (side by side)
| Feature | Nephritic | Nephrotic |
|---|---|---|
| Main lesion | Glomerular inflammation (endothelial and mesangial) | Podocyte injury, leaky filter |
| Onset | Often abrupt | Usually insidious |
| Haematuria | Prominent; red cell casts | Usually absent or slight |
| Proteinuria | Mild to moderate (<3.5 g/day) | Heavy (>3.5 g/day) |
| Oedema | Mild, periorbital | Marked, generalised |
| Blood pressure | Raised | Often normal early |
| Urine volume | Oliguria | Usually normal |
| Serum creatinine | Rises | Often normal at first |
| Serum albumin | Normal or slightly low | Low |
| Lipids | Normal | High cholesterol and triglycerides |
| Urine sediment | Red cell casts, dysmorphic red cells | Fatty casts, oval fat bodies |
| Complement | Low in some causes | Usually normal (except lupus, MPGN) |
| Typical example | Post-streptococcal GN | Minimal change disease |
Red cell casts, even a single one, mean the bleeding is from the glomerulus. Dysmorphic (misshapen) red cells point the same way.
Oedema occurs in both. In nephritic syndrome it comes from salt and water retention (low GFR); in nephrotic syndrome it comes mostly from low albumin plus renal sodium retention.
Lab abnormalities
Urine
| Test | Nephritic | Nephrotic |
|---|---|---|
| Dipstick blood | Strongly positive | Negative or trace |
| Dipstick protein | + to ++ | +++ to ++++ (frothy) |
| Microscopy | Red cell casts, dysmorphic red cells, granular casts | Fatty casts, oval fat bodies (show a "Maltese cross" under polarised light), hyaline casts |
| Protein quantity | Usually <3.5 g/day | >3.5 g/day |
| Selectivity | Non-selective | Selective (albumin only) in minimal change disease |
Quantifying protein. The random urine protein:creatinine ratio (uPCR) has largely replaced the 24-hour collection. Roughly, uPCR in mg/mmol × 10 = mg protein per day. A uPCR above about 350 mg/mmol fits nephrotic range, and above 200 mg/mmol usually means glomerular disease. Healthy people lose only a trace of protein in the urine (albumin well under 30 mg a day).
uPCR = 450 mg/mmol
Estimated daily protein ≈ 450 × 10 = 4500 mg ≈ 4.5 g/day
More than 3.5 g/day → nephrotic-range proteinuria
Blood
| Test | Nephritic | Nephrotic |
|---|---|---|
| Urea and creatinine | Raised | Often normal early |
| Albumin | Normal or mildly low | Low |
| Cholesterol, triglycerides | Normal | Raised (LDL up) |
| Complement (C3, C4) | Low in PSGN, lupus, MPGN, cryoglobulinaemia | Usually normal |
| ASO titre, anti-DNase B | Raised after streptococcal infection | Normal |
| Others | ANA, anti-dsDNA, ANCA, anti-GBM, cryoglobulins, hepatitis serology | Glucose/HbA1c, anti-PLA2R (membranous), serum and urine electrophoresis (myeloma, amyloid), hepatitis and HIV serology |
| Clotting | Normal | Hypercoagulable (low antithrombin, high fibrinogen) |
| Total calcium | Normal | Low (albumin-bound fraction falls) |
Complement as a sorting tool
| Low complement | Normal complement |
|---|---|
| Post-streptococcal / post-infectious GN (low C3, recovers in weeks) | IgA nephropathy and IgA vasculitis |
| Lupus nephritis (low C3 and C4) | Anti-GBM disease |
| Membranoproliferative GN (C3 nephritic factor) | ANCA vasculitis (pauci-immune) |
| Cryoglobulinaemia (very low C4) | Minimal change, FSGS, membranous |
| Infective endocarditis, shunt nephritis | Alport syndrome |
Low C3 that returns to normal within weeks fits post-streptococcal GN; persistently low C3 suggests MPGN or lupus.
Low complement nephritis: "PLEMC" – Post-infectious, Lupus, Endocarditis/shunt, MPGN, Cryoglobulins.
Imaging and biopsy
- Ultrasound: kidney size, obstruction, and safe biopsy planning; usually normal size in acute disease.
- Renal biopsy (light microscopy, immunofluorescence and electron microscopy) gives the definitive diagnosis in most adults. It is often not needed in typical childhood nephrotic syndrome (presumed minimal change; treat with steroids) or typical post-streptococcal GN.
- Before biopsy: normal clotting, controlled blood pressure, two kidneys of reasonable size. Uncontrolled hypertension and a bleeding tendency are contraindications.
Pathophysiology in one paragraph
The glomerular filter has three layers: the fenestrated endothelium, the glomerular basement membrane (negatively charged by heparan sulphate) and the podocyte foot processes with their slit diaphragms (nephrin). Damage to podocytes (fusion or effacement of foot processes) lets protein through, giving nephrotic syndrome. Inflammation of endothelial and mesangial cells by immune complexes or antibodies narrows capillaries, lowers GFR and breaks capillary walls so red cells escape, giving nephritic syndrome. When all compartments are hit (lupus, MPGN, HSP), the picture is mixed.
Mixed nephritic–nephrotic pictures
- Membranoproliferative (mesangiocapillary) GN: "tram-track" basement membrane; low C3; hepatitis C, cryoglobulins.
- Lupus nephritis (classes III and IV especially).
- IgA vasculitis (HSP).
- Cryoglobulinaemic GN.
- Post-infectious GN can also give heavy proteinuria.
Diabetic nephropathy is nephrotic, not nephritic, though it causes hypertension and progressive CKD; active red cell casts in a diabetic should prompt a search for another cause.
Expect: a short vignette where you must name the syndrome (child with cola urine, high BP and periorbital puffiness after a sore throat = nephritic; frothy urine and generalised oedema with low albumin = nephrotic); the 3.5 g/day cut-off and uPCR equivalents; red cell casts as proof of glomerular bleeding; oval fat bodies and Maltese crosses; which diseases lower complement; the hypercoagulable state and infection risk of nephrotic syndrome; and which conditions give mixed features.
Quick revision
- Nephritic: haematuria + red cell casts, hypertension, oliguria, raised creatinine, mild proteinuria.
- Nephrotic: protein >3.5 g/day, low albumin, oedema, high lipids; fatty casts.
- uPCR × 10 ≈ mg protein/day; >350 mg/mmol ≈ nephrotic range.
- Red cell casts = glomerular disease.
- Low C3: post-infectious, lupus, MPGN, cryoglobulins, endocarditis.
- Normal C3: IgA, anti-GBM, ANCA, minimal change, FSGS, membranous.
- Mixed: lupus, MPGN, HSP, cryoglobulinaemia.
- Children: nephrotic = minimal change; nephritic = post-streptococcal.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine; Fundamentals of Pathology).
FAQ
Can a patient have both nephritic and nephrotic features?
Yes. Lupus nephritis, membranoproliferative GN, IgA vasculitis and cryoglobulinaemia often cause heavy proteinuria together with haematuria, hypertension and falling kidney function.
Why is blood pressure high in nephritic syndrome?
Inflamed glomeruli filter less, so the kidney retains salt and water, expanding the circulating volume.
What do oval fat bodies mean?
They are tubular cells or macrophages filled with lipid, seen when heavy proteinuria and high blood lipids cause lipiduria; they show Maltese crosses under polarised light and point to nephrotic syndrome.
Does every nephrotic patient need a biopsy?
Most adults do, but a typical child with nephrotic syndrome is first treated with steroids as presumed minimal change disease and biopsied only if they do not respond or have unusual features.