PA27.1-7 | Renal Pathology I: Glomerular Disease & Renal Failure — Glossary

Amyloidosis derived from serum amyloid A protein (an acute-phase reactant), complicating chronic inflammatory diseases (rheumatoid arthritis, tuberculosis, osteomyelitis, familial Mediterranean fever).

Sudden decline in kidney function defined as ≥0.3 mg/dL rise in creatinine within 48 hours or ≥1.5× baseline within 7 days; replaces the older term 'acute renal failure'.

The commonest cause of intrinsic AKI; patchy tubular epithelial necrosis due to ischaemia or nephrotoxins; characterised by FENa >2%, urine Na >40 mmol/L, and four clinical phases.

Proteins modified by non-enzymatic glycation in a hyperglycaemic environment; crosslink GBM collagen, stimulate mesangial matrix production, and activate macrophages via RAGE receptors, driving diabetic nephropathy.

Mnemonic for emergency dialysis indications: Acidosis (pH <7.1), Electrolytes (hyperkalaemia), Intoxication (dialysable toxins), Overload (pulmonary oedema), Uraemia (encephalopathy/pericarditis/bleeding).

Acute deterioration in renal function superimposed on pre-existing CKD; identifying and treating the reversible precipitant (dehydration, sepsis, nephrotoxins) can restore GFR to the prior CKD baseline.

Amyloidosis derived from immunoglobulin light chains (lambda > kappa), associated with multiple myeloma and plasma cell dyscrasias; involves kidney, heart, and peripheral nerves.

X-linked (COL4A5 mutation) or AR/AD (COL4A3/COL4A4) hereditary nephritis characterised by progressive GN, sensorineural hearing loss, and ocular abnormalities; EM shows GBM basket-weave splitting; IF is negative.

Deposition of insoluble β-pleated sheet fibrillar proteins in tissues; renal amyloidosis presents as nephrotic syndrome and is the leading cause of death in systemic amyloidosis; diagnosed by Congo red (apple-green birefringence on polarised light).

Autoantibody directed against the NC1 domain of the α3 chain of type IV collagen; causes Type I RPGN (anti-GBM disease) and Goodpasture syndrome; identified by linear IgG IF staining and serum ELISA.

A laboratory finding of elevated blood urea nitrogen and serum creatinine, indicating reduced glomerular filtration rate; may be pre-renal, intrinsic renal, or post-renal in origin.

An IgG autoantibody that stabilises the alternative pathway C3 convertase (C3bBb), causing persistent uncontrolled C3 consumption; responsible for dense deposit disease (MPGN Type II) and associated with lipodystrophy.

Renal tubular injury in multiple myeloma from precipitation of free light chains (Bence Jones proteins) into large, laminated, fractured tubular casts with surrounding giant cell reaction; the dominant cause of AKI in myeloma.

Abnormalities of kidney structure or function persisting for ≥3 months with health implications; staged G1–G5 by GFR using the KDIGO classification.

Histochemical stain for amyloid; deposits appear salmon-pink/orange on conventional light microscopy and show apple-green birefringence under polarised light due to the β-pleated sheet fibril arrangement.

A histological finding in RPGN consisting of proliferating parietal epithelial cells and macrophages filling Bowman space, compressing the glomerular tuft; indicates severe glomerular injury.

Condition in which immunoglobulins precipitate in cold (cryoglobulins); types II and III (mixed) are most commonly associated with hepatitis C and cause MPGN-like glomerulonephritis with intraluminal hyaline thrombi.

Glomerular injury complicating long-standing diabetes mellitus, characterised by GBM thickening, mesangial expansion, and ultimately Kimmelstiel-Wilson nodular glomerulosclerosis; the leading cause of ESRD globally.

LM finding in PSGN and other proliferative GN where glomeruli are enlarged and hypercellular due to proliferation of endothelial and mesangial cells plus neutrophil infiltration, filling and compressing capillary lumens.

Uniform global increase in mesangial matrix and GBM thickening affecting all glomeruli; commoner than nodular change in diabetic nephropathy but not specific to diabetes alone.

Phase 3 of ATN recovery where urine output rises sharply (>2 L/day) but regenerating tubules cannot yet concentrate urine or reabsorb electrolytes; hypokalaemia is the major hazard.

Irregularly shaped, spiky red blood cells distorted during passage through the damaged glomerular basement membrane; presence in urine (>5%) is highly specific for glomerulonephritis.

The gross pathological appearance in late CKD: bilaterally small (6–8 cm), contracted, granular-surfaced kidneys with cortical thinning; represents the common endpoint of any progressive nephropathy.

Glycoprotein hormone produced by peritubular fibroblasts of the kidney that stimulates red blood cell production; ↓EPO in CKD causes normocytic normochromic anaemia managed with synthetic EPO analogues.

Arteriolar wall destruction by plasma protein insudation producing bright eosinophilic granular necrosis on H&E; occurs in malignant hypertension, vasculitis (SLE class IV), and other acute vascular injuries.

Glomerular disease defined by focal (< all glomeruli) and segmental (< whole tuft) areas of sclerosis and hyalinosis; leading cause of primary nephrotic syndrome in adults; associated with HIV, heroin, obesity, and genetic podocin mutations.

Ultrastructural flattening and fusion of podocyte foot processes seen on electron microscopy; the hallmark of nephrotic-range proteinuria, most characteristically in minimal change disease.

The fraction of filtered sodium that is excreted in the urine; calculated as (Urine Na × Plasma Cr)/(Plasma Na × Urine Cr) × 100; <1% = prerenal, >2% = ATN.

Simultaneous positivity for IgG, IgA, IgM, C3, C4, and C1q on renal immunofluorescence; virtually diagnostic of lupus nephritis, reflecting multi-isotype immune complex deposition.

Structurally aberrant IgA1 with undergalactosylated O-linked oligosaccharide chains in the hinge region; the primary pathogenic molecule in IgA nephropathy, recognised as foreign and targeted by IgG autoantibodies.

The middle layer of the filtration barrier, composed of type IV collagen, laminin, and heparan sulphate proteoglycans; provides both a size barrier and a charge barrier against anionic proteins such as albumin.

Irreversible obliteration of glomerular capillary loops by hyaline or fibrous material; the hallmark of CKD at the microscopic level; may be global (all loops) or segmental.

A tuft of fenestrated capillaries at the proximal end of the nephron, enclosed in Bowman capsule, responsible for generating the ultrafiltrate.

Anti-GBM antibody disease presenting with pulmonary haemorrhage plus rapidly progressive GN; caused by IgG autoantibodies against the NC1 domain of the α3 chain of type IV collagen.

IgA-dominant systemic small-vessel vasculitis affecting skin, gut, joints, and kidneys; renal biopsy shows mesangial IgA deposits identical to IgA nephropathy; most common vasculitis in children.

Deposition of homogeneous, glassy, eosinophilic material in the intima and media of arterioles due to plasma protein insudation and smooth muscle degeneration; the hallmark vascular lesion of benign hypertension and diabetes (both afferent and efferent in DM).

Compensatory increase in single-nephron GFR in surviving nephrons after nephron loss; initially maintains total GFR but causes intraglomerular hypertension and progressive glomerulosclerosis.

Concentric laminated proliferation of smooth muscle cells and collagen in interlobular arteries, creating an onion-skin appearance on histology; the hallmark arterial lesion of malignant hypertension.

The commonest primary GN worldwide, characterised by dominant mesangial IgA deposits; caused by galactose-deficient IgA1 immune complexes; presents with synpharyngitic haematuria and normal complement.

Systemic form of IgA nephropathy characterised by identical mesangial IgA deposits plus palpable purpura (legs/buttocks), arthralgia, and abdominal pain; the renal histology is indistinguishable from isolated IgA nephropathy.

Collagen deposition in the renal interstitium replacing atrophied nephrons in CKD; driven by TGF-β; correlates better with GFR decline than glomerulosclerosis alone.

International Society of Nephrology/Renal Pathology Society classification of lupus nephritis into six classes (I–VI) based on the site (mesangial, endocapillary, subepithelial) and extent (<50% vs ≥50% glomeruli) of immune complex involvement.

A specialised structure at the vascular pole of the glomerulus comprising JG cells (renin-secreting, in afferent arteriole), macula densa (NaCl-sensing DCT cells), and lacis cells; regulates GFR and RAAS.

International CKD staging system: G1 (≥90), G2 (60–89), G3a (45–59), G3b (30–44), G4 (15–29), G5 (<15 mL/min/1.73 m²); combined with albuminuria category for risk stratification.

Pathognomonic lesion of diabetic nephropathy: ovoid, PAS-positive, acellular hyaline nodule in the peripheral mesangium surrounded by a halo of patent capillary loops; represents extreme mesangial matrix accumulation.

Oval to spherical nodular accumulation of mesangial matrix in the periphery of the glomerulus in diabetic nephropathy; pathognomonic of diabetic glomerulosclerosis when present; seen in < 20% of diabetic renal biopsies.

Pathognomonic nodular glomerulosclerosis of diabetic nephropathy; PAS-positive acellular deposits in peripheral mesangium on light microscopy, best seen with PAS or silver stain.

Glomerulonephritis in systemic lupus erythematosus caused by immune complex (anti-dsDNA) deposition in the glomerulus; classified ISN/RPS classes I–VI based on site and extent of injury.

A plaque of specialised, closely packed cells in the distal convoluted tubule at the vascular pole of the glomerulus; senses luminal NaCl concentration and signals JG cells to adjust renin secretion.

Renal injury from severely elevated blood pressure (typically >200/120 mmHg) characterised by fibrinoid necrosis of arterioles, hyperplastic (onion-skin) arteriolitis in arteries, and a flea-bitten cortical appearance; presents as acute kidney injury.

The central connective tissue scaffold of the glomerular capillary tuft, comprising mesangial cells and matrix; supports capillaries, clears immune complexes, and expands in diabetic nephropathy.

Urinary albumin excretion of 30–300 mg/day (or ACR 3–30 mg/mmol); the earliest clinical marker of diabetic nephropathy, corresponding to Mogensen stage III.

A clinical syndrome of glomerular inflammation characterised by haematuria (with RBC casts), mild-to-moderate proteinuria, hypertension, oliguria, and azotaemia.

The structural and functional unit of the kidney, comprising the glomerulus, Bowman capsule, and the renal tubule (PCT, loop of Henle, DCT, collecting duct); approximately one million per kidney.

A clinical syndrome of glomerular permselectivity failure characterised by massive proteinuria (>3.5 g/day), hypoalbuminaemia, generalised oedema, hyperlipidaemia, and lipiduria.

Phase 2 of ATN characterised by urine output <400 mL/day and peak metabolic derangements (hyperkalaemia, acidosis, uraemia); typically lasts 10–14 days.

Lipid-laden renal tubular cells or free lipid droplets in urine, derived from filtered lipoproteins in nephrotic syndrome; show a Maltese cross birefringence pattern under polarised light.

Histopathological scoring system for IgA nephropathy on renal biopsy: Mesangial hypercellularity (M0/1), Endocapillary proliferation (E0/1), Segmental sclerosis (S0/1), Tubular atrophy/interstitial fibrosis (T0/1/2), Crescents (C0/1/2); predicts risk of ESRD.

Crescentic GN (Type III RPGN) with little or no immunoglobulin deposition on IF (pauci = few/scarce); associated with ANCA (MPO or PR3); encompasses microscopic polyangiitis and granulomatosis with polyangiitis.

A podocyte surface antigen targeted by IgG autoantibodies in ~75% of primary membranous nephropathy cases; serum anti-PLA2R titre is used to diagnose primary MN, monitor treatment response, and predict relapse.

Specialised visceral epithelial cells of the glomerulus whose interdigitating foot processes form the slit diaphragm; foot process effacement is the ultrastructural hallmark of nephrotic-range proteinuria.

AKI caused by reduced renal perfusion (not structural damage); tubules are intact and avidly reabsorb sodium (FENa <1%); fully reversible if perfusion is restored quickly.

A nephritic syndrome that deteriorates to renal failure within weeks to months; defined histologically by crescents in >50% of glomeruli formed by proliferating parietal epithelial cells.

A urinary cast containing red blood cells; pathognomonic of glomerulonephritis, indicating haemorrhage through the damaged glomerular capillary wall into the tubule.

Cylindrical aggregates of red blood cells moulded in the tubular lumen; their presence in urine sediment is pathognomonic of glomerulonephritis and distinguishes glomerular from non-glomerular haematuria.

Bone disease in CKD driven by ↓1,25(OH)₂D3, hypocalcaemia, and ↑PTH; manifests as osteitis fibrosa cystica (cortical bone resorption), osteomalacia, and vascular calcification.

Collective term for haemodialysis, peritoneal dialysis, and kidney transplantation; indicated in stage G5 CKD or when AEIOU criteria are met in AKI.

Reactive elevation of PTH in CKD due to hypocalcaemia (from ↓active vitamin D) and hyperphosphataemia; leads to renal osteodystrophy including osteitis fibrosa cystica.

The protein bridge (principally nephrin) spanning the space between adjacent podocyte foot processes; forms the final molecular gate of the glomerular filtration barrier.

In membranous nephropathy, the appearance of GBM spikes projecting between subepithelial immune-complex deposits ('domes') on silver methenamine stain, resembling a spiny cactus.

Large, dome-shaped electron-dense deposits on the epithelial (urinary) side of the GBM, visible only on EM; the pathognomonic ultrastructural finding of post-streptococcal GN.

Macroscopic haematuria occurring simultaneously with (within 1-3 days of) a mucosal infection, most characteristically pharyngitis; the clinical hallmark of IgA nephropathy distinguishing it from the 1-3 week latency of PSGN.

A glycoprotein secreted by cells of the thick ascending limb of Henle; forms the matrix scaffold of all urinary casts.

Group of conditions (HUS, TTP) characterised by platelet-fibrin microthrombi in glomerular capillaries and arterioles, microangiopathic haemolytic anaemia, thrombocytopaenia, and acute kidney injury.

Microscopic appearance in CKD where atrophied tubules fill with colloid-like pink casts, mimicking thyroid follicles; a marker of severe tubular atrophy.

Appearance of the GBM on PAS or silver stain in MPGN where mesangial cell interposition creates a second inner GBM layer, resembling two parallel tram rails; pathognomonic of MPGN on LM.

The clinical syndrome caused by accumulation of nitrogenous waste products and metabolic derangements when GFR falls below approximately 10–15 mL/min; features include encephalopathy, pericarditis, anaemia, platelet dysfunction, and metabolic acidosis.

Serofibrinous pericarditis in severe uraemia producing a rough 'bread-and-butter' texture on gross examination; presents with chest pain and pericardial friction rub; an absolute indication for dialysis.

A cylindrical structure formed in the renal tubule lumen when proteins or cells precipitate within the Tamm-Horsfall protein matrix; cast composition identifies the zone and nature of renal injury.

Straight capillaries that descend alongside the loop of Henle into the renal medulla; maintain the osmotic concentration gradient by countercurrent exchange; their sparse flow makes the medulla vulnerable to ischaemia.

A broad, homogeneous urinary cast with a waxy, refractile appearance; forms in dilated, atrophic tubules and indicates advanced chronic kidney disease.

Massive subendothelial immune complex deposits in lupus nephritis class IV appearing as eosinophilic, homogeneous thickening of capillary walls on H&E/PAS, resembling a wire loop; marker of severe active disease.