34 terms

Path 69: Nephritic Disorders

Nephritic syndrome
hematuria, proteinuria, hypertension -> Always acute
Urine sediment in nephritic syndrome
RBCs or RBC casts, granular casts, variable proteinuria, possibly WBCs
RBC casts
specific for hematuria caused by glomerular disease
Normal complement levels
IgA nephropathy/Henoch-Schonlein Purpura, Alport's syndrome (hereditary nephritis), SLE (class I, II, V)
Low complement levels
Post-streptococcal glomerulonephritis, membranoproliferative GN, SLE (class III, IV), bacterial endocarditis/infected ventriculoatrial shunt, cryoglobinemia
Variable complement
rapidly progressive glomerulonephritis
IgA nephropathy
most common type of glomerulonephritis -> peak in 2nd and 3rd decades -> high in Asians and Caucasians (rare in blacks) -> episodes of GROSS HEMATURIA (associated with viral respiratory or GI illness) -> persistent MICROSCOPIC HEMATURIA between these episodes -> usually non-nephrotic range PROTEINURIA (<3.5g/day), normal C3/C4
IgA nephropathy
generally a prolonged benign course but 20% of patients will progress to ESRD, most cases are clinically restricted to kidney, can be associated with arthritis, vasculitis, non-thrombocytopenic purpura (Henoch-Schonlein Purpura/HSP),
Conditions that can cause IgA nephropathy
hepatic cirrhosis, gluten enteropathy, HIV infection, minimal change disease, others (membranous GN, Wegener's, ankylosing spondylitis, small cell CA)
IgA nephropathy pathogenesis
production of IgA IC (polymeric IgA1 subclass -> derived from mucosal immune system) -> hematuria worsens during URI or GI infections -> predilection for mesangium (unknown why -> most likely due to deposition with activation of complement)
IGA nephropathy pathology
LM: segmental areas of increased mesangial matrix and hypercellularity); IF: mesangial and subendothelial deposits of IgA and C3 (+/- IgG and IgM); EM: Mesangial (most) and Subendothelial deposits
Post-streptococcal glomerulonephritis
manifests 10 days following pharyngitis or 3 weeks after impetigo (late period of antibody formation), more common in children (6-10) -> usually abrupt onset of nephritic syndrome with proteinuria >2g/day, complement levels ALWAYS LOW
Post-strep GN
diagnose by history and clinical presentation, elevated titers of anti-streptolysin O Ab or anti-DNAase B in association with low complement -> don't need to biopsy unless course of disease is abnormal
Post-strep GN
renal failure in 1%, may develop renal insufficiency 10-40 years after initial illness -> some glomeruli irreversibly damaged during acute episode -> results in compensatory hyperfiltration in remaining glomeruli in order to maintain normal GFR -> long standing increase in glomerular capillary pressure eventually results in hemodynamic mediated injury and glomerulosclerosis
PSGN pathogenesis
patient infected with nephritogenic strain of b-hemolytic strep -> antibody formation against streptococcal antigen component are circulating or planted in glomeruli -> subendothelial IC deposits activate complement (influx of inflammatory cells with resultant proliferative GN and decline in GFR) -> deposits rapidly cleared to resolve -> usually not seen by time biopsy is performed -> later characteristic subepithelial HUMPS are responsible for epithelial cell damage and proteinuria -> IC deposits cleared slowly (separated from circulation by GBM -> limits clearance)
PSGN pathology
LM = hypercellular glomeruli (neutrophils and monocytes), proliferation of mesangial, endothelial and epithelial cells, process is diffuse (entire lobules of all glomeruli) -> closure of capillary loops due to proliferation and swelling of endothelial cells and leukocytes infiltration; IF = granular deposits of IgG and C3 in the mesangium and along capillary walls; EM = electron dense deposits in subepithelial space -> HUMPS
Membranoproliferative glomerulonephritis (MPGN)
thickening of basement membrane, mesangial proliferation, infiltration of inflammatory cells -> primary (idiopathic) or secondary (underlying systemic disorder) -> has same histological findings -> 3 types have same pattern on LM but differentiated on basis of EM and IF
LM = mesangial expansion and hypercellularity -> thickening of the peripheral capillary loops due to double contour formation (TRAM TRACK) duplication of GBM -> EM: type 1 = subendothelial deposits, type II = deposition of dense material along GBM (unknown composition -> intra basement membrane causes splitting), type III = subendothelial, mesangial, subepithelial deposits
MPGN type I
most common -> idiopathic rare, secondary more common (Look for disease) -> lupus, hepatitis C, cryoglobinemia, endocarditis, parasitic infection -> subendothelial deposits splitting basement membrane -> activates classical complement activity (low complement)
very rare form of MPGN -> via alternate pathway -> C4 levels may be normal but C3 remains depressed due to C3 nephritic factor (IgG molecule that binds to and stabilizes C3bBb convertase allowing for continuous degradation of C3)
MPGN clinical
presents before age 30 in 4 different ways -> hematuria or proteinuria discovered on urinalysis; acute nephritic syndrome with hematuria and edema/HTN; recurrent episodes of gross hematuria; insidious onset of edema and nephrotic syndrome -> MOST progress to ESRD in 10-15 years
Rapidly progressive GN/crescentic GN
rapid decline in renal function with associated severe oliguria and if untreated death from renal failure in weeks-months -> renal biopsy and serologic analysis are indicated for diagnosis -> 3 subclass types (I, II, III)
LM = proliferative GN with prominent CRESCENT formation in 30-70% of glomeruli and +/- segmental necrosis -> histological appearance same regardless of cause -> crescents evolve from cellular to fibrocellular to fibrous crescents (differs prognosis -> cellular = reversible)
Focal segmental necrotizing and crescentic GN -> IF
Type I (20%) shows linear staining, anti GBM disease (Goodpasture's -> lung hemorrhage, idiopathic -> no lung hemorrhage); Type II (40%) shows granular staining, immune complex disease (SLE, post-infectious, IgA, Henoch-Schonlein, cryoglobulinemia, idiopathic); Type III (40%) shows no staining, Pauci-Immune GN (Wegener's, microscopic PAN, Churg-Strauss, idiopathic)
if only kidney = idiopathic, if systemic necrotizing arteritis = microscopic PAN, if pulmonary necrotizing granulomas = Wegener's
RPGN clinical
severe glomerular injury -> proteinuria (non-nephrotic), hematuria, RBC casts, HTN, edema, variable degree of oliguria -> 75% die or are placed on dialysis within 2 years of diagnosis -> best prognosis is treatable underlying disorder (SLE), or those that spontaneously remit (post-strep)
25-50% of patients have clinical renal disease on onset, 60% of adults patients develop renal disease during course -> immune mediated glomerular disease, abnormal excess production of antibodies against endogenous nuclear antigens (dsDNA, ANA, SM, RNA, Ro, La) -> ICs deposited in the kidney with subsequent complement activation, recruitment of inflammatory cells and tissue destruction
Lupus nephritis class I
minimal mesangial -> LM is normal, IF and EM show mesangial immune deposits
Lupus nephritis class II
mesangial proliferative -> mesangial immune deposits resulting in expansion and hypercellularity -> mild disease, microscopic hematuria, proteinuria, nephrotic syndrome/renal insufficiency are rare -> mimics IgA
Lupus nephritis class III
focal segmental proliferative < 50% of glomeruli affected on LM -> subendothelial and mesangial IC deposits -> complement activation and influx of inflammatory cells -> hematuria, nephrotic syndrome, HTN, renal failure
Lupus nephritis class IV
diffuse proliferative lupus nephritis >50% of glomeruli affected on LM -> marked deposition of IC in subendothelial and mesangium -> crescents and necrotizing lesions -> MOST COMMON AND MOST SEVERE form -> hematuria, proteinuria, nephrotic syndrome, renal failure, low complement, high anti-DNA levels
Lupus nephritis class V
membranous lupus nephritis -> subepithelial IC deposits, diffuse thickening of GBM -> same clinical course as idiopathic membranous GPN (can't differentiate) -> nephrotic syndrome, bland urine sediment, mild renal insufficiency, normal C3/C4, negative anti-DNA, IC deposits in blood vessels
Class VI lupus nephritis
advanced sclerosing lupus nephritis -> global sclerosis of >90% of glomeruli -> advanced interstitial fibrosis and tubular atrophy -> represents healing of prior inflammatory injury, advanced stages of chronic class III, IV and V
Lupus nephritis
clinical course follows protracted course with periods of remissions and exacerbations -> disease activity and flares can be monitored by serial measurement of compliments, anti-dsDNA Ab, ESR, CRP