Brozna Clin Man 4 Flashcards
prototypic example of nephritic syndrome
Acute postinfectious glomerulonephritis
prototypic example of nephritic syndrome
Rapidly progressive glomerulonephritis-
nephritic syndrome and rapid loss of renal function
Rapidly progressive glomerulonephritis
(Clinical term with multiple etiologies and disease entities)
Renal failure over days to weeks Proteinuria usually less than 3 g/day Hematuria with red cell casts May have features of vasculitis Blood pressure often normal
Rapidly Progressive Crescentic Glomerulonephritis (RPCGN)
The presenting complaints may be similar to those in severe postinfectious glomerulonephritis: Acute onset of macroscopic hematuria, Decreased urine output, Hypertension Edema.
More commonly, however, RPGN has an insidious *onset with the initial symptoms being fatigue or edema
Untreated RPGN–> end-stage renal disease
(Prednisone, immunosuppressive agents, plasmapheresis)
Syndrome
Multiple etiologies: anti-glomerular basement membrane, pauci-immune RPGN, immune complex deposition
Anti-glomerular Basement Membrane Antibody Mediated RPGN
= (Goodpasture Disease)
- Rare
- Autoantibody to intrinsic glomerular basement membrane antigens (non- collagenous region of type IV collagen chain α3)
- proteinuria and nephritic sediment
- ~50% will have pulmonary hemorrhage (alveolar basement membrane)
- Genetic predisposition (HLA-DRB1)
- Frequent rapid progression to oliguria and renal failure
- Poor prognosis without treatment (plasmapheresis and immunosuppression treatment)
Pathology:
Diffuse proliferative glomerulonephritis with ** crescent formation, glomerular sclerosis and tubular loss
Immunohistology
** Linear deposits of complement fixing IgG = pathognomonic
Rapidly Progressive Crescentic Glomerulonephritis (RPGN)- Pauci-immune
no detectable anti-GBM or immune complexes (50%) (Most have anti-neutrophil cytoplasmic autoantibodies (ANCA))
Immune complex deposition mediated disease (45%)
Systemic vasculitides include:
* Granulomatosis with polyangiitis (Wegener’s granulomatosis)
Microscopic polyangiitis
* Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
Most common cause for the renal component of pulmonary-renal vasculitic syndrome
Most common cause of death in pauci-immune RPGN
Anti-neutrophilic cytoplasmic antibody autoantibodies that react with antigens in the cytoplasm of neutrophils are frequently associated with systemic vasculitis
Massive pulmonary hemorrhage is the most common cause of death in patients presenting with ANCA-associated disease. However, once immunosuppressive therapy has begun, infection is more common.
Hallmark histologic lesions of pauci-immune
crescents and fibrinoid necrosis
ANCA
Immune complex mediated RPGN
Can be a complication of any immune complex nephritides including:
Postinfectious glomerulonephritis
Lupus nephritis
IgA nephropathy
Henoch-Schönlein purpura (immunoglobulin A and systemic vasculitis)
Systemic Lupus ErythematosusImmune Complex and Autoantibody Disease
Autoimmune
multiple organ systems
Failure of the mechanisms
that maintain self tolerance
Renal Disease in Systemic Lupus Erythematosus
range from asymptomatic microhematuria and mild proteinuria to full-blown nephrotic syndrome or rapidly progressive renal failure
Pattern of glomerular injury seen in systemic lupus erythematosus and other immune complex renal diseases are primarily related to the site of formation of the immune deposits***
~50% of patients with SLE will have clinical renal disease
Approximately 10% progress to end-stage renal disease
> 90% patients have positive ANA
IgG immune deposits dominant immunoglobulin
C1q and C4 immune deposits frequently present
Glomerulonephritis
Tubulointerstitial nephritis
Immunoglobulin microvascular thrombi
Subendothelial immune deposits (no inflammation)
Glomerular deposits in SLE
Glomerular deposits (IgG, IgA, IgM, C3, C1q)
Deposits simultaneously in
Mesangium
Sub epithelial
Subendothelial
Extra-glomerular immune type deposits
Tubular basement membrane
Interstitium
Blood vessels
Wire loop goes with
lupus
Classification of Lupus Immune complex Mediated Glomerular Disease
Minimal mesangial lupus nephritis (class I) Mesangioproliferative this nephritis (class II) Focal lupus nephritis (class III) Diffuse lupus glomerulonephritis (most common and severe) (class IV) Lupus membranous glomerulonephritis (class V)
Diffuse Proliferative Lupus Nephritis
Class IV
Marked increase in cellularity. Glomerulus size greatly enlarged. The large, markedly cellular glomerulus appears “stuffed” into Bowman’s capsule with a resultant decrease in urinary space
Glomerular capillary walls are segmentally thickened by wire-loop deposits. An intraluminal deposit forms a “hyaline thrombus” in one capillary, and there is global endocapillary proliferation
Chronic Kidney Disease- most common causes
Diabetes mellitus and hypertension account for 70% of patients with ESRD In the United States
Primary glomerulonephritis may be the most common cause ESRD outside of North America Europe and Australia
Chronic Glomerulonephritis
Chronic glomerulonephritis refers to the late phase of glomerulonephritis that progresses to renal impairment and eventual failure (ESRD)
If not diagnosed early, patients often present with established hypertension, proteinuria and renal impairment
Chronic primary glomerulonephritis accounts for ~10% of end-stage renal disease in the United States
Chronic Kidney Disease Risk Factors
Diabetes mellitus High blood pressure A family history of kidney disease African-American and other ethnic minorities Obesity Smoking Older age Having protein in the urine Having autoimmune diseases such as lupus
Chronic Kidney Disease and Uremia
Clinical syndrome associated with progressive loss of renal function and the accumulation of metabolic waste products
Azotemia
No single uremic toxin has been identified that can account for all clinical manifestations of uremia
Complications can include nausea, vomiting, fatigue, pruritus, seizure, encephalopathy, bleeding disorders, pleuritic, pericarditis, polyneuropathy
Therapy includes renal replacement therapy
ie. Dialysis or transplantation
Uremic Pericarditis
Histopathology:
Fibrinous, aseptic inflammation (predominantly lymphocytic) is the hallmark of uremic pericarditis
Causes of Primary Chronic GlomerulonephritisDescending Order of Incidence
Rapidly progressive glomerulonephritis Focal segmental glomerular sclerosis Membranoproliferative glomerulonephritis Membranous glomerulopathy IgA nephropathy
Diabetes Mellitus
Diabetes mellitus
Disorder of glucose metabolism resulting in hyperglycemia
Long-term complications (15-20 years after onset) Accelerated atherosclerosis Diabetic nephropathy Diabetic retinopathy Diabetic neuropathy
Clinical diagnosis
***Glycated hemoglobin (A1C) (less than 5.7&)
Fasting plasma glucose less than 100 mg/dl
Diabetic nephropathy
It appears that in patients with type 2 diabetes, renal structural changes are more heterogeneous and diabetic glomerulopathy lesions less severe than in type 1 patients with similar urine albumin levels.
In type 2 diabetes, a reduced GFR in the presence of a normal albumin excretion rate is a common finding.
Subset had typical diabetic glomerulopathy,
Remaining patients had predominantly tubulointerstitial and vascular changes
Leading cause of chronic kidney failure in the United States
Advanced kidney disease occurs in ~40% of insulin-dependent type I and type II diabetics
Natural history of DN–> Relentless decline in GFR
In type 1 diabetic patients glycemic control slows the progression of diabetic nephropathy
Elevated systemic blood pressure appears to accelerate the progression of diabetic nephropathy
Diabetic Nephropathy Pathogenesis
Two major processes play key pathophysiologic roles as diabetic glomerular lesions develop:
A metabolic defect linked to hyperglycemia and advanced glycosylation end products produces thickened GBM and increased mesangial matrix
Hemodynamic effects associated with glomerular hypertrophy also contribute to the development of glomerulosclerosis
Diabetic NephropathyPathologic Features
Glomerular basement membrane thickening Tubular basement membrane thickening Diffuse mesangial sclerosis Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) Arteriolar hyalinosis
RENAL AMYLOIDOSIS
Amyloidosis term to refer to extracellular tissue deposition of low molecular weight protein fibrils
Associated with number of inherited inflammatory disorders in which extracellular deposits of fibrillary proteins are responsible for tissue damage
Amyloid IgG light chain (AL) and amyloid associated (AA) non-IG protein become insoluble because of abnormal folding and deposit as fibrils in extracellular tissues
Kidneys, heart, liver, central nervous system, peripheral nerves, musculoskeletal, lung, skin… can have amyloid deposits
Nonselective proteinuria, with or without nephrotic syndrome is the most common manifestation of renal involvement by amyloidosis.
Fibrillary Glomerulonephritis
Diagnosis based on electron microscopy showing randomly arranged non-branching fibrils in glomerular mesangium / capillary walls
Pathogenesis is unknown (associated with malignancy, monoclonal myopathy, hepatitis C or autoimmune diseases)
Patients can present with mixture of nephrotic and nephritic syndrome features
Immunofluorescence positive for IgG, C3, polyclonal light chains
~50% progress to end-stage renal disease within 2-6 years
Glomerulonephritis Associated with Bacterial Endocarditis and Other Systemic Infections
Bacterial infection related immune complex mediated glomerulonephritis
Endocarditis, infected spinal fluid ventriculoatrial shunt
Associated with Staphylococcus aureus, Streptococcus viridans, staphylococcus epidermidis
Histologic findings similar to poststreptococcal glomerulonephritis or membranoproliferative glomerulonephritis
Clinical manifestations include hematuria, red cell casts, hypertension and renal insufficiency
30% patients with shunt nephritis develop nephrotic syndrome
Glomerulonephritis Associated with Essential Mixed Cryoglobulinemia
Vasculitis caused by the deposition of circulating cryoglobulins that contain both IgG and IgM Rheumatoid Factor directed against the IgG
Most patients have chronic hepatitis C virus infection (HBV and HIV)
HCV-containing immune complexes may play a direct role in the pathogenesis of the renal disease
20 - 30% associated with membranoproliferative glomerulonephritis Type I
Microscopic hematuria 41%
Nephrotic syndrome 22%
Nephritic syndrome 14%
Hypertension 65%
Associated with small vessel leukocytoclastic vasculitis (Skin)
Palpable purpura
