Glomerulonephritis and renal disease
Renal disorders: glomerulonephritis, nephrotic syndrome, nephropathy, stones and tumours
Kidney disease for FCPS Part 1: filtration barrier, nephritic and nephrotic syndromes, diabetic nephropathy, infection, stones, cysts and tumours. Each urine and biopsy picture is linked to its mechanism and imaging.
The filtration barrier
- Three layers: fenestrated endothelium, the glomerular basement membrane and podocyte foot processes with their slit diaphragms (nephrin).
- Proteins are held back by size (slit diaphragm is the final size barrier) and by charge: the GBM and podocyte coat are rich in negatively charged heparan sulfate, which repels negatively charged albumin. Loss of this charge (minimal change disease) lets albumin through selectively.
Nephritic and nephrotic patterns
| Feature | Nephritic | Nephrotic |
|---|---|---|
| Lesion | Inflammation damages the capillary wall | Podocyte or basement membrane leak |
| Urine | Red cell casts (the hallmark of glomerulonephritis: red cells leak through a damaged glomerulus and are moulded in tubules), haematuria, some protein | Protein over 3.5 g/day, fatty casts |
| Oedema | Renal salt and water retention | Low albumin (low oncotic pressure) plus renal sodium retention |
| Other | Hypertension, oliguria | Hyperlipidaemia, thrombosis, infection |
- Hyperlipidaemia in nephrotic syndrome: low oncotic pressure stimulates increased hepatic lipoprotein synthesis, and lipoprotein lipase activity falls; it settles when proteinuria remits.
- Urinary loss of antithrombin causes thrombosis (renal vein thrombosis, worst in membranous); loss of IgG (hypogammaglobulinaemia) gives pneumococcal peritonitis.
| Most common | Disease |
|---|---|
| Nephrotic syndrome in children | Minimal change disease |
| Nephrotic syndrome in adults | Membranous (FSGS in some populations) |
| Nephritic syndrome in children | Post-streptococcal GN |
| Glomerulonephritis in adults worldwide | IgA nephropathy |
| Intrinsic acute kidney injury | Acute tubular necrosis |
Glomerular diseases
| Disease | Setting | Biopsy |
|---|---|---|
| Minimal change | Child; steroid-responsive | Normal light microscopy; foot process effacement |
| FSGS | Adults, HIV (collapsing), heroin, obesity | Segmental sclerosis |
| Membranous | Adult; anti-PLA2R in primary disease; secondary to hepatitis B, SLE, drugs, cancer | Thick capillary walls, spikes on silver stain, granular subepithelial IgG |
| Post-streptococcal | 1–2 weeks after throat infection or 3–6 weeks after skin infection; low C3, raised ASO or anti-DNase B | Subepithelial humps |
| IgA nephropathy | Haematuria 1–2 days after a respiratory infection | Mesangial IgA deposits |
| Lupus nephritis, MPGN type I | SLE; hepatitis C | Subendothelial deposits (wire loops) |
| Goodpasture (anti-GBM) | Haemoptysis and haematuria | Crescentic (extracapillary) GN with linear IgG along the GBM against type IV collagen α3 |
| Alport | X-linked, deafness, lens changes | Split, basket-weave GBM; type IV collagen α5 |
| Pre-eclampsia | Proteinuria in pregnancy | Glomerular endotheliosis |
- Anti-PLA2R antibodies bind the phospholipase A2 receptor on podocytes and form subepithelial immune complexes in primary membranous nephropathy; a negative test does not exclude it (other antigens such as THSD7A).
Diabetic and hypertensive kidney
- Diabetic nephropathy: hyperfiltration, then microalbuminuria, then proteinuria. Biopsy: thick GBM, mesangial expansion and rounded, acellular, PAS-positive Kimmelstiel–Wilson nodules with capillary loops stretched around them; Congo red negative (separates it from amyloid). Kidneys stay normal or large (12 cm or more) even with poor function.
- Benign nephrosclerosis: hyaline arteriolosclerosis; symmetrically small kidneys. Malignant hypertension: onion-skin arterioles, flea-bitten kidney.
- Renal artery stenosis: atheroma in the proximal 2 cm (ostium) in elderly arteriopaths; fibromuscular dysplasia (string of beads) in young women.
- Anaemia of chronic kidney disease: normocytic, normochromic, mainly from erythropoietin deficiency (peritubular fibroblasts lost), plus shortened red cell life.
Infection and interstitial disease
- Ascending infection: E. coli with P fimbriae. Acute pyelonephritis (fever, rigors, loin pain) damages the parenchyma; CT shows striated wedges of low enhancement.
- Reflux nephropathy: polar scars over clubbed calyces. Haematogenous abscess: S. aureus.
- Papillary necrosis: analgesics, sickle cell, diabetes, obstruction with infection.
- Acute interstitial nephritis: drugs; eosinophils, white cell casts.
Calculi
| Stone | Cause | Imaging |
|---|---|---|
| Calcium oxalate (commonest) | Low urine volume, hypercalciuria, enteric hyperoxaluria | Radio-opaque |
| Calcium phosphate | Distal RTA, hyperparathyroidism | Nephrocalcinosis |
| Struvite | Urease organisms (Proteus) | Staghorn |
| Uric acid | Gout, acid urine | Radiolucent, seen on CT |
| Cystine | Autosomal recessive | Faintly opaque |
- Commonest site of obstruction: the vesicoureteric junction. Pain from a stone in the lower ureter is referred to the groin, testis or labium (genitofemoral nerve, L1–L2).
- Unilateral hydronephrosis in a child: commonest cause pelviureteric junction obstruction (dilated pelvis, normal ureter, sometimes a crossing vessel).
Cystic disease
- ADPKD: PKD1 (chromosome 16); huge cystic kidneys, liver cysts, berry aneurysms; tolvaptan slows cyst growth.
- ARPKD: PKHD1; large uniformly bright fetal kidneys, oligohydramnios, hepatic fibrosis.
- Multicystic dysplastic kidney: non-communicating cysts.
Tumours
| Tumour | Key points |
|---|---|
| Renal cell carcinoma | From proximal tubule; clear cells look empty because their abundant lipid and glycogen dissolve during processing; VHL loss (3p); smokers; haematuria, mass, polycythaemia, left varicocele; spreads mainly by blood, growing into the renal vein and IVC (cannonball lung metastases) |
| Angiomyolipoma | Fat (negative HU); tuberous sclerosis |
| Wilms tumour | Child; claw sign; WT1 |
| Neuroblastoma | Crosses midline, calcified, encases vessels |
| Urothelial carcinoma | Whole urothelium at risk; aniline dyes, smoking; schistosomiasis gives squamous carcinoma |
- Clear cytoplasm alone is not diagnostic: adrenal cortical and some ovarian tumours look similar.
Remember Humps mean post-streptococcal; spikes mean membranous; nodules mean diabetes; linear IgG means anti-GBM.
Exam trap Large kidneys on ultrasound do not mean good function in diabetic nephropathy.
Exam trap Red cell casts point to the glomerulus; white cell casts point to the interstitium.
How FCPS asks about this
- Red blood cell casts: glomerulonephritis.
- Spikes and subepithelial IgG with negative secondary screen: primary membranous nephropathy, anti-PLA2R.
- High cholesterol in untreated nephrotic syndrome: increased hepatic lipoprotein synthesis.
- PAS-positive, Congo red-negative mesangial nodules: nodular diabetic glomerulosclerosis.
- Haemoptysis, haematuria, linear IgG, crescents: Goodpasture syndrome.
- Why RCC cells look clear: lipid and glycogen dissolved in processing.
- Commonest nephrotic syndrome in children: minimal change disease.
Test yourself on this topic
5 of the 46 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A 55-year-old woman with type 2 diabetes for 20 years has proteinuria of 3 g/day. Her kidneys are of normal size. Renal biopsy shows rounded, acellular, PAS-positive mesangial nodules with capillary loops stretched around them; Congo red stain is negative. What is the diagnosis?
Answer: Nodular diabetic glomerulosclerosis
Kimmelstiel-Wilson nodules are rounded accumulations of mesangial matrix, PAS-positive and acellular, with the capillary loops pushed to the periphery; they are characteristic of diabetic nephropathy. They follow diffuse mesangial expansion and basement membrane thickening caused by non-enzymatic glycation and growth factor activity. In diabetic nephropathy the kidneys stay normal-sized or enlarged even when function falls. A negative Congo red stain excludes amyloid, which can also form nodules.
Kimmelstiel-Wilson nodules
- PAS-positive acellular mesangial nodules
- Capillary loops pushed to the edge
- Congo red negative (not amyloid)
- Kidneys normal or large in diabetes
Remember Diabetes, big kidneys, PAS nodules: Kimmelstiel-Wilson.
Exam trap Large kidneys on ultrasound do not mean preserved function in diabetic nephropathy.
Why the other options are wrong
- Renal AL amyloidosis Amyloid nodules stain with Congo red and show apple-green birefringence.
- Membranous nephropathy Shows thickened basement membranes with subepithelial spikes, not nodules.
- Focal segmental glomerulosclerosis Shows segmental scarring of some glomeruli, not nodules.
- Hypertensive nephrosclerosis Gives small kidneys with hyaline arteriolosclerosis and modest proteinuria.
A 65-year-old woman who started omeprazole 3 months ago has a creatinine that has risen over two weeks, a low-grade fever and a rash. Urine shows white cells and white cell casts but sterile culture, and blood eosinophils are raised. What is the most likely diagnosis?
Answer: Acute interstitial nephritis
Drugs such as proton pump inhibitors, NSAIDs and penicillins can provoke a T-cell-mediated hypersensitivity reaction in the renal interstitium. Biopsy shows interstitial oedema with lymphocytes, plasma cells and often eosinophils around the tubules (tubulitis). White cell casts with sterile urine, fever, rash and eosinophilia suggest the diagnosis; stopping the drug, sometimes with steroids, usually allows recovery.
Drug-induced interstitial nephritis
- PPIs, NSAIDs, penicillins
- White cell casts, sterile urine
- Fever, rash, eosinophilia
- Stop the drug; steroids may help
Remember Rising creatinine on a PPI with white cell casts: interstitial nephritis.
Exam trap PPI-related interstitial nephritis often lacks the classic rash and fever, so it is easily missed.
Why the other options are wrong
- Acute tubular necrosis Shows muddy brown granular casts, usually after ischaemia or toxins.
- Post-infectious glomerulonephritis Shows red cell casts, haematuria and low complement.
- Acute pyelonephritis Urine culture would be positive.
- Obstructive uropathy There would be hydronephrosis and no casts.
A 48-year-old man has nephrotic syndrome. Biopsy shows diffusely thickened capillary walls with spikes on silver stain and granular subepithelial IgG on immunofluorescence. Tests for hepatitis B, lupus and cancer are negative. Which serum antibody is most likely present?
Answer: Anti-phospholipase A2 receptor
Thickened capillary walls with spikes and granular subepithelial IgG are the picture of membranous nephropathy, the commonest cause of nephrotic syndrome in adults in many populations. In about 70 to 80% of primary cases, circulating IgG4 antibodies bind the phospholipase A2 receptor on podocytes, forming immune deposits in situ beneath the podocytes. Complement activation damages the podocytes and causes heavy proteinuria. The antibody level helps diagnosis and tracks response to treatment.
Membranous nephropathy
- Thick capillary walls, spikes on silver
- Subepithelial granular IgG
- Primary: anti-PLA2R antibodies
- Risk of renal vein thrombosis
Remember Adult nephrotic with spikes: check anti-PLA2R.
Exam trap A negative anti-PLA2R does not exclude primary disease; other antigens such as THSD7A exist.
Why the other options are wrong
- Anti-glomerular basement membrane Gives linear IgG and a crescentic nephritis, not subepithelial deposits.
- Anti-double-stranded DNA Seen in lupus nephritis, which has been excluded.
- Anti-neutrophil cytoplasmic antibody Seen in pauci-immune vasculitis with crescents and few deposits.
- Anti-streptolysin O Points to post-streptococcal disease with subepithelial humps and a nephritic picture.
A 30-year-old man who injects drugs has fever and left flank pain. Urine culture is sterile, but blood cultures grow Gram-positive cocci in clusters, and a 3 cm abscess is found in the cortex of the left kidney. How did the infection most likely reach the kidney?
Answer: Haematogenous seeding of the renal cortex
Staphylococcus aureus from skin or an infected injection site enters the blood and seeds the richly perfused renal cortex, forming a cortical abscess (renal carbuncle). Because the infection is in the parenchyma rather than the urinary tract, urine cultures are often sterile at first. Ascending infection, usually with Gram-negative organisms such as E. coli, begins in the medulla and pelvis and gives positive urine cultures. CT shows a rim-enhancing, low-density collection.
Renal cortical abscess
- Staphylococcus aureus in the blood
- Seeds the renal cortex
- Urine culture often sterile
- Ascending infection: Gram-negative, medulla
Remember Gram-positive abscess with sterile urine: it came through the blood.
Exam trap Look for endocarditis in an injecting drug user with S. aureus renal abscesses.
Why the other options are wrong
- Ascent from the bladder up the ureter Ascending infection is usually Gram-negative with positive urine culture.
- Lymphatic spread from the colon Not a recognised route to the kidney.
- Direct spread from a psoas abscess There is no psoas collection; spread usually goes the other way.
- Reflux of infected urine into tubules Reflux causes ascending pyelonephritis with Gram-negative bacteria.
A 58-year-old smoker has a 6 cm renal mass removed. Histology shows sheets of polygonal cells with empty-looking clear cytoplasm and a delicate branching vascular network. What makes the cytoplasm look clear on routine sections?
Answer: Lipid and glycogen dissolved in processing
Clear cell renal carcinoma, the commonest renal cancer, arises from proximal tubular cells. Loss of the VHL gene stabilises hypoxia-inducible factor, which drives angiogenesis and changes cell metabolism so that the cells store lipid and glycogen. Both are dissolved out during routine tissue processing, leaving the cytoplasm empty and clear. The rich, delicate vasculature produced by VEGF makes these tumours very vascular.
Clear cell RCC
- From proximal tubule
- VHL loss stabilises HIF
- Cells store lipid and glycogen
- Rich VEGF-driven vessels
Remember Clear cells are full of fat and sugar that wash out.
Exam trap Clear cells also occur in adrenal tumours and some ovarian tumours, so clear cytoplasm alone is not diagnostic.
Why the other options are wrong
- Abundant mucin that does not stain Renal cell carcinoma does not produce mucin.
- Cytoplasm packed with mitochondria This makes cells granular and pink, as in oncocytoma.
- Hydropic swelling from cell injury Hydropic change is a reversible injury pattern, not the tumour's appearance.
- Large amounts of intracellular keratin Keratin gives pink cytoplasm in squamous cells.
Where this sits in the CPSP syllabus
- Diagnostic Radiology, Paper 2: Abdominal, renal and reproductive disorders, Renal disorders: glomerular, diabetic and hypertensive nephropathy, infection, calculi, tumours