The Approach to Glomerular

The contract between this chapter and the reader.

1. 1. Recognise the clinical syndromes of glomerular disease.
2. 2. Define and characterise the nephrotic syndrome.
3. 3. Define and characterise the nephritic syndrome.
4. 4. Recognise rapidly progressive GN as an emergency.
5. 5. Use urinalysis and the sediment to localise injury.
6. 6. Quantify proteinuria and interpret it.
7. 7. Use the serologic panel to point to a mechanism.
8. 8. Interpret the complement pattern.
9. 9. Decide when a renal biopsy is needed.

A sixty-second reading. Each bullet stands alone.

• Glomerular disease presents as recognisable syndromes that guide the workup.
• The nephrotic syndrome is heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia, with a bland sediment.
• The nephritic syndrome is hematuria with dysmorphic red cells and casts, hypertension, and reduced GFR.
• Rapidly progressive GN is a nephritic picture with rapid loss of function over days to weeks — an emergency.
• Asymptomatic urinary abnormalities and chronic glomerulonephritis are the milder and later presentations.
• Urinalysis and the sediment are the key bedside test: dysmorphic red cells and red-cell casts mean glomerular bleeding.
• Proteinuria is quantified by a urine protein- or albumin-to-creatinine ratio; nephrotic-range exceeds 3.5 grams per day.
• The serologic panel — ANA, ANCA, anti-GBM, complement, anti-PLA2R, light chains — points to the mechanism.
• A low complement narrows the differential to lupus, post-infectious GN, MPGN/C3 glomerulopathy, and cryoglobulinemia.
• Anti-PLA2R points to membranous nephropathy; ANCA and anti-GBM to crescentic disease.
• The renal biopsy is usually the definitive test when the diagnosis is unclear and would change management.
• Biopsy may be deferred in typical childhood minimal change disease and classic diabetic nephropathy.
• The approach narrows from syndrome to mechanism to diagnosis.

The medical core. An expert should agree the approach to glomerular disease is fully covered here.

Why it matters at the bedside

Glomerular disease announces itself in a handful of patterns, and the clinician who recognises the pattern is already halfway to the diagnosis. The method is disciplined and the same every time: read the syndrome from the history and the urine, let the serology point to a mechanism, and — when it matters — confirm with a biopsy. Pattern, then mechanism, then diagnosis.

The clinical syndromes

• Glomerular disease clusters into five syndromes: the nephrotic syndrome, the nephritic syndrome, rapidly progressive glomerulonephritis, asymptomatic urinary abnormalities, and chronic glomerulonephritis. They overlap, and they guide rather than replace the biopsy — but naming the syndrome focuses everything that follows.

The nephrotic syndrome

• The nephrotic syndrome is the podocyte's signature: heavy proteinuria (over 3.5 grams a day), hypoalbuminemia, oedema, and hyperlipidemia, with a bland urinary sediment. It carries its own complications — a hypercoagulable, thrombosis-prone state, infection risk, and acute kidney injury. Its causes are the podocytopathies and membranous nephropathy: minimal change, FSGS, membranous, diabetic, and amyloid disease.

The nephritic syndrome

• The nephritic syndrome is the signature of inflammatory, proliferative injury: haematuria with dysmorphic red cells and red-cell casts, sub-nephrotic proteinuria, hypertension, oedema, and a reduced GFR. The red-cell cast is the giveaway that the blood is glomerular. Its causes are the proliferative glomerulonephritides: IgA, post-infectious, lupus, and MPGN.

Rapidly progressive GN

• When a nephritic picture is accompanied by a rapid loss of kidney function over days to weeks, it is rapidly progressive glomerulonephritis — a renal emergency, the clinical face of crescentic disease. Its three mechanisms map to the three immunofluorescence patterns: anti-GBM (linear), ANCA (pauci-immune), and immune-complex (granular). It must be recognised fast, because crescents fibrose.

The milder and chronic presentations

• Two quieter presentations complete the set. Asymptomatic urinary abnormalities — isolated microscopic haematuria and/or low-grade proteinuria — may reflect thin basement membrane disease or early IgA nephropathy. And chronic glomerulonephritis presents late, as slowly progressive chronic kidney disease with proteinuria and haematuria, often when much of the kidney is already scarred.

Urinalysis and the sediment

• Urinalysis with microscopy of the sediment is the indispensable bedside test, and often the most informative single investigation. Dysmorphic red cells and red-cell casts mean glomerular bleeding (nephritic); a bland sediment with heavy proteinuria points to podocyte/barrier injury (nephrotic); oval fat bodies and lipiduria accompany nephrotic-range protein loss. The sediment localises the injury before any blood test returns.

Quantifying proteinuria

• Proteinuria must be quantified, not just detected: a urine protein-to-creatinine or albumin-to-creatinine ratio (or a timed collection) gives the figure, and nephrotic-range proteinuria exceeds about 3.5 grams a day. The degree of proteinuria both classifies the syndrome and tracks the disease and its response to treatment.

The serologic panel and complement

• A targeted serologic panel points to the mechanism: ANA and anti-dsDNA (lupus), ANCA (vasculitis), anti-GBM (anti-GBM disease), anti-PLA2R (membranous), complement C3/C4, hepatitis serologies, and serum protein electrophoresis with free light chains (paraprotein disease). The complement pattern is especially useful — a low complement narrows the field to lupus, post-infectious GN, MPGN/C3 glomerulopathy, and cryoglobulinemia, while most other glomerular diseases run a normal complement.

When to biopsy

• The renal biopsy is usually the definitive test (its own chapter), and the principle is simple: biopsy when the diagnosis is unclear and the result would change management — most adult nephrotic syndrome, nephritic and rapidly progressive disease, unexplained AKI or proteinuria, and suspected systemic disease. Biopsy is reasonably deferred in a few settings: typical childhood minimal change disease (treated empirically), classic diabetic nephropathy (long-standing diabetes with retinopathy and a typical course), sometimes anti-PLA2R-positive membranous, and where there is a contraindication.

Putting it together

• The whole approach is a funnel. The syndrome — read from history, sediment, and quantified proteinuria — sets the broad category; the serology points to a mechanism within it; and the biopsy confirms the diagnosis and grades it. Pattern narrows to mechanism narrows to diagnosis, and only then to treatment. That discipline is what turns a confusing presentation into a managed disease.

Five fully-built tables.

Table A — The clinical syndromes

Table B — Nephrotic versus nephritic

Table C — Urinalysis and the sediment

Table D — The serologic panel

Table E — When to biopsy

Visualise & Map

Causal chains, each ending in a named action.

Chain 1 — Nephrotic

Podocyte/barrier injury → heavy proteinuria, hypoalbuminemia, edema → the nephrotic syndrome → ACTION: run the nephrotic workup (podocytopathies, membranous).

Chain 2 — Nephritic

Inflammatory/proliferative injury → haematuria with red-cell casts, hypertension, reduced GFR → the nephritic syndrome → ACTION: run the nephritic workup (proliferative GN).

Chain 3 — Rapidly progressive

Severe injury → crescents → rapid loss of GFR → rapidly progressive GN → ACTION: urgent biopsy and treatment (a renal emergency).

Chain 4 — The complement clue

Immune-complex/complement-consuming disease → complement is consumed → a low serum complement → ACTION: narrow to lupus, post-infectious, MPGN/C3, or cryoglobulinemia.

Chain 5 — The funnel

Syndrome (sediment + proteinuria) → serology (mechanism) → a focused differential → ACTION: biopsy to confirm, then treat.

Numbered rules. These numbers are the cross-reference handle for the cases and flowcharts.

Clinical Reasoning

Five cases. Each stops you at a decision before it answers it.

Every mechanism from Level 3 earns a bedside consequence and an action.

Exhaustive. Every rule in the chapter is here.

Safety & Evidence

Panel A — Red flags

Panel B — NEVER DO

Anti-patterns clinicians fall into. Each becomes a Level 22 distractor.

The grade reflects strength of evidence, not importance.

Apply & Test

Pre-rounds compression. Rules only.

Active recall. At least one card per objective.

Micro-teaching for rounds. Two scenarios, five steps each.

Nine items, each anchored in this chapter. At least one per objective.