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Flashcards in Brozna Clin Man 4 Deck (28):
1

prototypic example of nephritic syndrome

Acute postinfectious glomerulonephritis
prototypic example of nephritic syndrome

Rapidly progressive glomerulonephritis-
nephritic syndrome and rapid loss of renal function

2

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

3

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

4

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

5

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

6

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.

7

Hallmark histologic lesions of pauci-immune

crescents and fibrinoid necrosis

ANCA

8

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)

9

Systemic Lupus ErythematosusImmune Complex and Autoantibody Disease

Autoimmune
multiple organ systems

Failure of the mechanisms
that maintain self tolerance

10

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)

11

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

12

Wire loop goes with

lupus

13

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)

14

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

15

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

16

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

17

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

18

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

19

Uremic Pericarditis

Histopathology:
Fibrinous, aseptic inflammation (predominantly lymphocytic) is the hallmark of uremic pericarditis

20

Causes of Primary Chronic GlomerulonephritisDescending Order of Incidence

Rapidly progressive glomerulonephritis
Focal segmental glomerular sclerosis
Membranoproliferative glomerulonephritis
Membranous glomerulopathy
IgA nephropathy

21

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

22

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

23

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

24

Diabetic NephropathyPathologic Features

Glomerular basement membrane thickening
Tubular basement membrane thickening
Diffuse mesangial sclerosis
Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules)
Arteriolar hyalinosis

25

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.

26

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

27

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

28

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