Renal diseases
Per disease
ΡΑ: rare. Focal proliferative, mesangial proliferative, membranous, secondary amyloidosis, IgA
nephritis, rheumatoid vasculitis [crescentic / necrotizing]. Can be p-ANCA (+): pauci-immune. From
medication (gold, D-penicillamine, CyA, MTX, NSAID [TIN, ATN], TNFis).
Sjögren: usually TIN (- RTA), rarely GN (MPGN, membranous, mesangial proliferative, focal crescentic ±
cryoglobulinemia).
SLE: GN, TMA, renal vein thrombosis, vasculitis of the kidney, TIN, drug-induced
AS: IgAN, amyloidosis, drug-induced (NSAIDs).
PsA: usually membranous or FSGS
ReA: IgAN (microscopic hematuria)
Takayasu: renal artery stenosis → ΑΥ
AAV: pauci-immune, segmental necrotizing GN ± crescent (not proliferative). IF: granular deposits, in
Goodpasture linear deposits. GPA may lead rapidly to AKI (especially in crescentic form).
PAN: renal and interlobar arteries (medium-sized, muscular arteries) or even the smaller arcuate
arteries. Microaneurysm formation and wedge-shaped infarctions.
Cryoglobulinemia: MPGN. Histo Dx: i) intraluminal hyaline thrombi (composed of precipitated
cryoglobulins), ii) diffuse IgM deposition in the capillary loops / granular IC deposition iii)
subendothelial deposits presenting a crystalloid aspect on electron microscopy.
IgA vasculitis: mesangial proliferative (with crescents in 40%) and mesangial IgA deposition.
Also, focal/diffuse proliferation??
MCTD: kidney involvement in 25% (although many are asymptomatic; severe disease is rare),
membranous, mesangial, hypertensive crises (as in SRC).
Behçet: less frequent compared to other vasculitides. Membranous or focal/diffuse proliferative.
Amyloidosis. Intrarenal microaneurysms.
Gout: chronic urate nephropathy, acute UA nephropathy, UA nephrolithiasis.
SSc: TMA-SRC: progressive thickening of the walls + narrowing of the vascular lumen of arteries →
hypertension, ischemic kidney disease. SRC: AKI + hypertension + relatively bland urinary sediment.
FMF: amyloidosis, PAN (renal artery microaneurysms).
IgG4-RD: TIN with low C3.
Myositis: AKI due to rhabdomyolysis, sometimes mesangial proliferative GN.
Sarcoidosis: TIN+ granulomas, hypercalcemic nephrolithiasis, obstructive uropathy by retroperitoneal
lymph node enlargement.
AA-amyloidosis: nephrotic syndrome + progressive renal failure. The kidneys tend to be larger than
expected (on u/s) because of amyloid deposition. On light microscopy, amyloid fibrils are seen
deposited within the mesangial regions and demonstrate apple green birefringence under polarized
light in tissue stained with Congo red. Amyloid can also infiltrate the tubulointerstitial compartment
and lead to renal tubular defects. RA, JIA, AS, PsA, FMF.
Post-streptococcal: diffuse proliferative with both subendothelial and subepithelial deposits
(“humps”), RPGN.
•Necrotizing: usually small or medium-size vasculitides: AAV, LCV, IgAV, PAN, Kawasaki, secondary (ex.
SLE). Means fibrinoid necrosis of the vessel wall. Exception: TAO.
•Granulomatous: large-vessel, GPA, sarcoidosis, PVCNS. In GPA and sarcoidosis the granulomas are
found in the tissue while in GCA within the vessel wall.
NOTES
If the biopsy is positive for immunoglobulin (± complement) deposition, focus on distinguishing
between infection-associated monoclonal, IC-autoimmune diseases and deposition diseases.
Complement is typically normal in anti-GBM and in pauci-immune GN but low in IC-mediated GN (with
the exception of IgAN because IgA doesn’t activate complement) and IgG4-RD TIN, LN.
, IgA nephropathy is the most common GN.
Rapidly progressive GN (or crescentic) is a clinical term. (Goodpasture, AAV, SLE, IgAV).
In nephrotic syndrome there is a significant loss of albumin and maybe also β-region and complement
factors (but α2-macroglobulin might be normal or increased - is too large to be lost in urine). Because
of low albumin, liver compensates the loss of oncotic pressure by rising the synthesis of other proteins,
like lipoproteins (→ explain hyperlipidemia of nephrotic).
Diabetic nephropathy: usually glomerulosclerosis + podocytopathy.
Proteinuria discovered by a semiquantitative urine dipstick typically reflects glomerular proteinuria
because the dipstick recognizes albumin (therefore in cases of MM and light chain excretion, stick
might be normal).
In Dx of glomerular hematuria, don’t forget ‘thin basement membrane nephropathy’, a familial, benign
condition, treated with ACEis.
Pathophysiology: one of the targets is the GBM itself or some antigen trapped within it, as in post-
streptococcal disease. Such antigen-antibody reactions can be systemic, with GN occurring as one of
the components of the disease process, such as in SLE or IgAN. On the other hand, in small vessel
vasculitis, cell-mediated immune reactions are the main culprit instead of antigen-antibody reactions.
Here, T-cells and macrophages flood the glomeruli with resultant damage.
Etiology of GN is based on the underlying mechanism:
i) immune complex–mediated
ii) ANCA-associated
iii) anti-GBM
iv) monoclonal immunoglobulin-mediated
v) C3 glomerulopathy
vi) mesangial depositions (IgAN, amyloidosis)
vii) podocytopathy
The severity of the GN is revealed by the pattern of injury, such as crescentic, necrotizing, diffuse
proliferative, exudative, membranoproliferative, mesangial proliferative or sclerosing.
The chronicity of GN is determined by evaluating the extent of glomerulosclerosis, tubular atrophy and
interstitial fibrosis and vascular sclerosis present on the biopsy.
Secondary diagnosis either related or unrelated to the GN, such as diabetic glomerulosclerosis, ATN or
TMA, may also be present.
Normal 24h urine protein: <150mg (≈20mg being albumin). Microalbiminuria: albumin (only) loss 30-
300mg/24h, proteinuria>150mg/24h, nephrotic> 3.5gr/24h. Cases of increased urine protein:
pregnancy, ↑GFR (hyperfiltration), UTI, fever (↑ permeability).
↑GFR causes: pregnancy, recovery from AKI (polyuric phase), hyperthyroidism,
compensatory (early diabetic nephropathy, after nephrectomy), dopamine (in diuretic dose-renal
vasodilation).
The urine protein-to-creatinine ratio (UPCR) is a key measure in evaluating kidney function and
proteinuria. Normal UPCR <0.2, nephrotic >3.0
Creatinine measurement: serum Cr is a fairly insensitive indicator of early decline in GFR. Cr is freely
filtered across the glomerulus and another 10-20% is also secreted by the proximal tubule. When GFR
falls, the rise in serum Cr is counteracted by increased tubular creatinine secretion. In addition,
hemodynamic changes, such as those caused by treatment with ACEis or NSAIDs, are a common cause
of changes in serum Cr levels in the absence of progression of underlying renal disease. 24h urine
Per disease
ΡΑ: rare. Focal proliferative, mesangial proliferative, membranous, secondary amyloidosis, IgA
nephritis, rheumatoid vasculitis [crescentic / necrotizing]. Can be p-ANCA (+): pauci-immune. From
medication (gold, D-penicillamine, CyA, MTX, NSAID [TIN, ATN], TNFis).
Sjögren: usually TIN (- RTA), rarely GN (MPGN, membranous, mesangial proliferative, focal crescentic ±
cryoglobulinemia).
SLE: GN, TMA, renal vein thrombosis, vasculitis of the kidney, TIN, drug-induced
AS: IgAN, amyloidosis, drug-induced (NSAIDs).
PsA: usually membranous or FSGS
ReA: IgAN (microscopic hematuria)
Takayasu: renal artery stenosis → ΑΥ
AAV: pauci-immune, segmental necrotizing GN ± crescent (not proliferative). IF: granular deposits, in
Goodpasture linear deposits. GPA may lead rapidly to AKI (especially in crescentic form).
PAN: renal and interlobar arteries (medium-sized, muscular arteries) or even the smaller arcuate
arteries. Microaneurysm formation and wedge-shaped infarctions.
Cryoglobulinemia: MPGN. Histo Dx: i) intraluminal hyaline thrombi (composed of precipitated
cryoglobulins), ii) diffuse IgM deposition in the capillary loops / granular IC deposition iii)
subendothelial deposits presenting a crystalloid aspect on electron microscopy.
IgA vasculitis: mesangial proliferative (with crescents in 40%) and mesangial IgA deposition.
Also, focal/diffuse proliferation??
MCTD: kidney involvement in 25% (although many are asymptomatic; severe disease is rare),
membranous, mesangial, hypertensive crises (as in SRC).
Behçet: less frequent compared to other vasculitides. Membranous or focal/diffuse proliferative.
Amyloidosis. Intrarenal microaneurysms.
Gout: chronic urate nephropathy, acute UA nephropathy, UA nephrolithiasis.
SSc: TMA-SRC: progressive thickening of the walls + narrowing of the vascular lumen of arteries →
hypertension, ischemic kidney disease. SRC: AKI + hypertension + relatively bland urinary sediment.
FMF: amyloidosis, PAN (renal artery microaneurysms).
IgG4-RD: TIN with low C3.
Myositis: AKI due to rhabdomyolysis, sometimes mesangial proliferative GN.
Sarcoidosis: TIN+ granulomas, hypercalcemic nephrolithiasis, obstructive uropathy by retroperitoneal
lymph node enlargement.
AA-amyloidosis: nephrotic syndrome + progressive renal failure. The kidneys tend to be larger than
expected (on u/s) because of amyloid deposition. On light microscopy, amyloid fibrils are seen
deposited within the mesangial regions and demonstrate apple green birefringence under polarized
light in tissue stained with Congo red. Amyloid can also infiltrate the tubulointerstitial compartment
and lead to renal tubular defects. RA, JIA, AS, PsA, FMF.
Post-streptococcal: diffuse proliferative with both subendothelial and subepithelial deposits
(“humps”), RPGN.
•Necrotizing: usually small or medium-size vasculitides: AAV, LCV, IgAV, PAN, Kawasaki, secondary (ex.
SLE). Means fibrinoid necrosis of the vessel wall. Exception: TAO.
•Granulomatous: large-vessel, GPA, sarcoidosis, PVCNS. In GPA and sarcoidosis the granulomas are
found in the tissue while in GCA within the vessel wall.
NOTES
If the biopsy is positive for immunoglobulin (± complement) deposition, focus on distinguishing
between infection-associated monoclonal, IC-autoimmune diseases and deposition diseases.
Complement is typically normal in anti-GBM and in pauci-immune GN but low in IC-mediated GN (with
the exception of IgAN because IgA doesn’t activate complement) and IgG4-RD TIN, LN.
, IgA nephropathy is the most common GN.
Rapidly progressive GN (or crescentic) is a clinical term. (Goodpasture, AAV, SLE, IgAV).
In nephrotic syndrome there is a significant loss of albumin and maybe also β-region and complement
factors (but α2-macroglobulin might be normal or increased - is too large to be lost in urine). Because
of low albumin, liver compensates the loss of oncotic pressure by rising the synthesis of other proteins,
like lipoproteins (→ explain hyperlipidemia of nephrotic).
Diabetic nephropathy: usually glomerulosclerosis + podocytopathy.
Proteinuria discovered by a semiquantitative urine dipstick typically reflects glomerular proteinuria
because the dipstick recognizes albumin (therefore in cases of MM and light chain excretion, stick
might be normal).
In Dx of glomerular hematuria, don’t forget ‘thin basement membrane nephropathy’, a familial, benign
condition, treated with ACEis.
Pathophysiology: one of the targets is the GBM itself or some antigen trapped within it, as in post-
streptococcal disease. Such antigen-antibody reactions can be systemic, with GN occurring as one of
the components of the disease process, such as in SLE or IgAN. On the other hand, in small vessel
vasculitis, cell-mediated immune reactions are the main culprit instead of antigen-antibody reactions.
Here, T-cells and macrophages flood the glomeruli with resultant damage.
Etiology of GN is based on the underlying mechanism:
i) immune complex–mediated
ii) ANCA-associated
iii) anti-GBM
iv) monoclonal immunoglobulin-mediated
v) C3 glomerulopathy
vi) mesangial depositions (IgAN, amyloidosis)
vii) podocytopathy
The severity of the GN is revealed by the pattern of injury, such as crescentic, necrotizing, diffuse
proliferative, exudative, membranoproliferative, mesangial proliferative or sclerosing.
The chronicity of GN is determined by evaluating the extent of glomerulosclerosis, tubular atrophy and
interstitial fibrosis and vascular sclerosis present on the biopsy.
Secondary diagnosis either related or unrelated to the GN, such as diabetic glomerulosclerosis, ATN or
TMA, may also be present.
Normal 24h urine protein: <150mg (≈20mg being albumin). Microalbiminuria: albumin (only) loss 30-
300mg/24h, proteinuria>150mg/24h, nephrotic> 3.5gr/24h. Cases of increased urine protein:
pregnancy, ↑GFR (hyperfiltration), UTI, fever (↑ permeability).
↑GFR causes: pregnancy, recovery from AKI (polyuric phase), hyperthyroidism,
compensatory (early diabetic nephropathy, after nephrectomy), dopamine (in diuretic dose-renal
vasodilation).
The urine protein-to-creatinine ratio (UPCR) is a key measure in evaluating kidney function and
proteinuria. Normal UPCR <0.2, nephrotic >3.0
Creatinine measurement: serum Cr is a fairly insensitive indicator of early decline in GFR. Cr is freely
filtered across the glomerulus and another 10-20% is also secreted by the proximal tubule. When GFR
falls, the rise in serum Cr is counteracted by increased tubular creatinine secretion. In addition,
hemodynamic changes, such as those caused by treatment with ACEis or NSAIDs, are a common cause
of changes in serum Cr levels in the absence of progression of underlying renal disease. 24h urine
