APPROACH TO THE
PATIENT WITH
GLOMERULAR DISEASES
Gülçin Kantarcı, MD
Professor of
Nephrology Department
OBJECTIVES (knowledge, skills and attitudes)
Knowledge:
At the end of this lecture the students
1.
Has a good understanding the diagnosis and the differential diagnosis of
Glomerular Diseases with their emergent treatment requirements and methods.
2.
Has a knowledge about diagnosis methods of Glomerular Diseases.
(Laboratuary tests, screening tests, other invasive and non-invasive medical
procedures)
Skills:
3.
Can name the possible diagnosis and make a differential diagnosis of
Glomerular Diseases .
4.
Can use the diagnosis methods for Glomerular Diseases economically and
properly.(Lab. tests, screening tests, other invasive and non-invasive medical
procedures)
5.
Can interpret the result of these test correctly.
6.
Can choose between emergent and non-emergent situations, and give
emergent treatment for diseases.
Attitudes:
7.
Presents a worthy thought, attitude and behavior appropriate for a physician in
patient communication.
REFERENCE
1.
Current Medical Diagnosis and Treatment, Maxine A.
Papadakis, Stephen J. McPhee, Eds. Michael W. Rabow, Associate Ed.
http://accessmedicine.com
Chapter 22. Glomerular Diseases
2.
Bates' Guide to Physical Examination & History Taking 11th
edition, Bickleys LS, Szilagyi PG; Lippincott Williams and Wilkins¸
3.
Kumar and Clark's Clinical Medicine, 8th edition; Kumar &
Clark, Elsevier
4.
Andreoli and Carpenter's Cecil Essentials of Medicine 8th
edition, Andreoli and Carpenter, Elsevier
PART 11: RENAL AND GENITOURINARY DISEASES 123: Glomerular
Disorders and Nephrotic Syndromes
Glomerulus
• Most glomerular diseases are immune-mediated, and
described as glomerulonephritis (GN).
GLOMERULAR INFLAMMATION AND INJURY
GLOMERULONEPHRITIS
Primary GN
• Minimal Change Disease
• FSGS
• Membranous GN
• Idiopatic MPGN
• IgA nephropathy
• Proliferatif GN
Sekonder GN
İnfective
 Fungi (Candida albicans,Coccidioides immitis)
 Rickettsiae
Connective tissue diseases
 Henoch-Schönlein purpura
 Polyarteritis nodosa
 SLE
 Wegener’s granulomatosis
Glomerular basement membrane diseases
 Goodpasture’s syndrome
Hematologic dyscrasias
 Mixed IgG-IgM cryoglobulinemia
 Serum sickness
 Thrombotic thrombocytopenic
 purpura–hemolyticuremic syndrome
Viral:
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Coxsackievirus
Cytomegalovirus
Epstein-Barr virus
Hepatitis B virus
Hepatitis C virus
Herpes zoster virus
Measles
Mumps
Varicella
GLOMERULAR DISEASES WITH
NEPHROTIC SYNDROME
Nephrotic synd: edema, Nephrotic-range
proteinuria) greater than 50 mg/kg per day or 40
mg/h/m2 in children and 3.5 g/24 h in adults ,
hyperlipidemia
• Minimal change disease (MCD)
• Focal Segmental Glomerulosclerosis (FSGS)
• Membranous nephropathy (MN)
MINIMAL CHANGE DISEASE (MCD)
• characterized initially by dramatic increases in glomerular
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•
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permeability in association with little or no structural
abnormalities by light microscopy.
lipoid nephrosis Munk (1913)
MCD is most common in children, In adults,especially in
elderlies associated with secondary causes
70% to 90% of cases of nephrotic syndrome in children
younger than age 10 years and 50% of cases in older
children.
Minimal change glomerulopathy also causes 10% to 15%
of cases of primary nephrotic syndrome in adults.
%15-20 nephritic features may occur
MCD in children mostly (%80-90) idiopatic
HISTOPATHOLOGY
• The principal target of injury is the podocyte,
***podocytopathies
• Light microscopy: lack of definitive alteration in glomerular
structure. Lipid droplets in the tubuler cells
• Immunofluorescence: also shows no change
• Electron mic: fusion of epithelial foot processes
Minimal-change disease (electron microscopy)
The glomerular basement membrane is normal;
the cytoplasm of the podocytes is vacuolated, with effacement of foot
processes and microvilli. Methenamine silver, 2800×.
Laboratory findings of MCD
• severe proteinuria.
• Microscopic hematuria is seen in fewer than 15% of patients.
• Volume contraction may lead to a rise in both the hematocrit and
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hemoglobin.
ESR is increased as a consequence of hyperfibrinogenemia as well as
hypoalbuminemia.
The serum albumin <2 g/dL and, in more severe cases, <1 g/dL.
Total cholesterol, LDL, and triglyceride levels are increased.
Pseudohyponatremia has been observed in the setting of marked
hyperlipidemia.
Renal function is usually normal, although a minority of patients have
substantial AKI.
IgG levels may be profoundly decreased—a factor that may result in
susceptibility to infections.
Complement levels are typically normal in patients with minimal change
glomerulopathy
Secondary causes of MCD
• Drugs
-NSAID
-penicillin
-trimetoprim
• Toxins
-Mercury
-lead
-bee stings
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•
•
Infection
-Mononucleosis
- HIV
- Immunizations
Tumors
-Hodgkins lymphoma
-other lymhoproliferative dis.,
-Carcinoma
Obesity
Specific treatment: corticosteroids
• Emprical steroid theraphy for children <10
• In children who have received empirical treatment, a renal
biopsy is indicated when there is failure to respond to a 4to 6-week course of prednisone.
• oral prednisone be administered as a single daily
dose starting at 60 mg/m2 /day
• or 2 mg/kg/day to a maximum 60 mg/day
Clinical course of MCD as related to
steroid theraphy
• STEROID-SENSITIVE NEPHROTIC SYNDROME
(SSNS)
- complete remission of proteinuria within 8-12 weeks with
infrequent relapses
• FREQUENTLY RELAPSING and STEROID
DEPENDENT (FR-SD)
-relapses occur during the taper of steroids
-relapses occur at rate of twice every 6 months or six
times every 18 months
-relapses occur within 2 weeks of cessation of theraphy
• STEROID-RESISTANT NEPHROTIC SYNDROME
(SRNS)
-Failure to obtain a remission within 12 weeks
PROGNOSIS
• In adults 85-90 % survival rate
• The potential efficacy of therapy must be considered in
relation to the natural history of the disease.
• Untreated idiopathic MCD was associated with a risk of
mortality due to infection and less commonly
thromboembolism
complications
• Related to persistent NS (peritonitis, ARF, CKD in
steroid resistant patients)
• Side effect of therapy( stra, cataracts, acne, cushingoid
face, hyperglisemia, HT)
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
(FSGS)
• an important lesion found to underly the nephrotic
syndrome in adults and a frequent lesion in children and
adolescents
• Pathology: a focal process; not all glomeruli are involved,
the glomeruli are segmentally sclerotic, and portions of
the involved glomeruli may appear normal by light
microscopy.
• Nonsclerotic glomeruli and segments usually have no
staining for immunoglobulins or complement.
• The ultrastructural features of FSGS on electron
microscopy include focal foot process effacement.
FSGS
histologic variants
NORMAL Glomerulus
Collapsing
Classical
Tip lesions
Laboratory findings
• Hypoproteinemia is common in patients with
FSGS and the serum albumin concentration may
fall to below 2 g/dL, especially in patients with the
collapsing variant.
• Hypogammaglobulinema and hyperlipidemia are
typical; serum complement components are
generally in the normal range.
• Serologic testing for HIV infection should be
obtained for all patients with FSGS, especially
those with the collapsing pattern.
Clinical manifestations
 peripheral edema,
 hypoalbuminemia, and
 nephrotic range proteinuria.
 Patients with FSGS also commonly have
hypertension, and many have microscopic
hematuria.
 The level of kidney function may vary.
The relative frequencies of clinical
manifestations :
 Nephrotic range proteinuria - 60 to 75 %
 Microscopic hematuria - 30 to 50 %
 Hypertension - 45 to 65 %
 Renal insufficiency - 25 to 50 %
PROGNOSIS OF FGS
• Untreated primary FSGS often follows a
progressive course to end-stage renal disease
(ESRD).
• The rate of spontaneous complete remission
among patients with nephrotic syndrome is
unknown, but is probably less than 10 percent.
• Spontaneous remission is more likely to occur
among patients with normal kidney function and
non-nephrotic proteinuria.
Response to therapy
• The strongest prognostic indicator is the
degrees of reduction in proteinuria
• complete response : <200 to 300 mg/day.
• partial response reduction ≥ 50 %
• relapse is return of proteinuria to ≥ 3.5 g/day
after a complete or partial remission.
• Steroid-dependence relapse while on therapy or
requirement for continuation of steroids
• Steroid-resistance little or no reduction in
proteinuria after 12 to 16 weeks of prednisone
therapy
Therapy of MCD & FSGS
• Prednisone theraphy: not to exceed 60 mg/day
• 50% responding 2-6 wk
• Cyclosporine therapy is the second choice for
FSGS
• ACEI may provide a substantial reduction in
proteinuria and a long-term renoprotective effect
that may be equal to,or greater than, that of
immunosuppressive therapy.
• Response rates to immunosuppressive therapy in
primary FSGS
45% for complete remission,
10% for partial remission,
45% for no response.
Membranous GN
• Idiopathic membranous glomerulopathy is the most common
cause of nephrotic syndrome in adults (25% of adult cases)
and can occur as an idiopathic (primary) or secondary
disease.
• Secondary membranous glomerulopathy is caused by
autoimmune diseases (e.g., lupus erythematosus,
autoimmune thyroiditis),infection (e.g., hepatitis B, hepatitis
C), drugs (e.g., penicillamine,gold), and malignancies (e.g.,
colon cancer, lung cancer).
Membranous GN
• In patients over the age of 60, membranous glomerulopathy is
associated with a malignancy in 20% to 30% of patients. The
peak incidence of membranous glomerulopathy is in the fourth
or fifth decade of life.
Pathology
• The characteristic histologic abnormality in MGN is diffuse
global capillary wall thickening and the presence of
subepithelial immune complex deposits.
The immun deposits of Ig G and complement
components develop on the subepithelial surface of the
glomerular capillary wall
spikes
Light microscopy in membranous nephropathy, uniform increase in the thickness of the
glomerular capillary walls throughout the glomerulus without any increase in glomerular
cellularity. Spikes of matrix emanating from the outer surface of the basement membrane
indicative of advanced MN are revealed by silver–methenamine stain (×400).
Conditions associated with (secondary)
MGN
group
common
uncommon
Immun dis.
SLE, DM
RA, Hashimoto’s dis.
Ankylosing spondylis.
Pr. Biliary cirrhosis
Infectious
HBV
HCV, malaria, syphilis
Drugs and toxins
Gold , NSAIDs
Mercury, captopril, formaldehyde
Miscellaous
Tumors, renal
transplant
Sarcoidosis,Sickle cell dis.
Clinical manifectations
• Nephrotic syndrome 80%
• Asymtomatic non-nephrotic proteinuria 20%
• Proteinuria (5-15 g/day)
• Microscobic hematuria may be seen 50% of adults
• Renal vein thrombosis 40%
• Renal function usually well preserved at the on set of dis.
Common secondary causes
• Membranous lupus nephritis (Class V)
• Hepatitis B
• Cancer (adults over 50 years incidence of malignancy in
MGN 20%)
• Renal allografts
Prognosis of pr. MGN
• Spontaneous complete remission of proteinuria occurs in
5 to 30 %
• Spontaneous partial remission (≤ 2 g of proteinuria per
day) occurs in 25 to 40 %
• ESRD in untreated patients is
 14 % at 5 years,
 35 % at 10 years,
 41 % at 15 years
Laboratory findings in MGN
• Proteinuria is usually more than 3 g of protein per 24 hours and
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may exceed 10 g/day in 30% of patients.
Microscopic hematuria is present in 30% to 50% of patients
Renal function is typically preserved at presentation.
Hypoalbuminemia is observed if proteinuria is severe.
Complement levels are normal; however, the complex of
terminal complement components known as C5b-9 is found in
the urine in some patients.
Tests for hepatitis B, hepatitis C, syphilis, and immunologic
disorders such as lupus, mixed connective tissue disease, and
cryoglobulinemia should be obtained to exclude secondary
causes.
Theraphy of MGN
• Supportive care including ACEI, lipid-lowering therapy
• Corticosteroids
• Alkylating agents (chlorambucil or cyclophosphamide),with
or without concurrent corticosteroid treatment
-Chlorambucil (0.2 mg/kg/day) or cyclophosphamide, alternating
monthly with daily prednisone(0.5 mg/kg/day), in combination with
intravenous pulse methylprednisolone(1 g/day) for the first 3 days of
each month
• Cyclosporine
• The high prevalence of deep vein thrombosis in patients
with membranous glomerulopathy (up to 45%) has led to the
use of prophylactic anticoagulation for patients with
proteinuria greater than 10 g/day
Management of MGN
• Adult patients with good prognostic features, with less than
4 g/day proteinuria and normal renal function, should be
managed conservatively.
• Patients at moderate risk (persistent proteinuria between 4
and 6 g/day after 6 months of conservative therapy and
normal renal function) or high risk of progression
(persistent proteinuria greater than 8 g/day with or without
renal insufficiency) should be considered for
immunosuppressive therapy
• Individuals who have advanced chronic kidney disease
and in whom serum creatinine exceeds 3 to 4 mg/dL are
best treated by supportive care awaiting dialysis and renal
transplantation
Membranoproliferative GN
(Mesangial Capillary Glomerulonephritis)
• MPGN is characterized by diffuse global capillary wall
thickening, frequently with a double contoured
appearance and either subendothelial deposits (type I
MPGN) or deposits within the mesangium and basement
membrane (type IIMPGN).
Clinical presentations of MPGN
• Nephrotic syndrome (50%)
• Combination of asymptomatic hematuria and proteinuria
(25%)
• Acute nephritic syndrome (25%)
• Hypertension is typically mild
• renal dysfunction occurs ( 50%)
Classification of MPGN
Histology of MPGN
light microscopy:
• thickening of the glomerular basement membrane
(GBM), due to immune complex deposition and to
interposition of the mesangial cell cytoplasm between the
GBM and the endothelial cell;
• hypercellularity, lobular appearance of the glomerular
tuft
lobular appearance of the glomerular tuft
increased glomerular cellularity
thickening of all capillary walls with
double contours, cellular proliferation
TYPES OF MPGN
Primary or idiopathic
• Type I: mesangiocapillary GN
• Type II: dense deposit disease
• Type III: an immune complex disease, similar to type 1.
Secondary (associated with other diseases)
With immun deposits
Infections –crioglobulinemia
- HBV,HCV, Endocarditis, Malaria, EBV,HIV,mycoplasma
Autoimmun diseases
-SLE,RA,Sjörgen’s syndrome
Dysproteinemia
-Light chain deposit dis.,Waldernstrom’s
macroglobulinemia, fibrilar
Without immun deposits
Chronic liver disease
-Cirrhosis, α1 antitripsin deficiency
Thrombotic microangiopathies
- HUS/TTP, Antiphospholipid antibody Syn,Sickle cell anemia
Laboratory findings
• Hematuria is the hallmark of patients presenting with MGPN,
• The degree of proteinuria varies widely.
• Renal insufficiency occurs in a variable number of cases, but it is
the most ominous feature of the acute nephritic syndrome.
• Serologic and clinical evidence of cryoglobulinemia,hepatitis C,
hepatitis B, osteomyelitis, subacute bacterial endocarditis, or
infected ventriculoatrial shunt should be sought in type I MGPN.
• C3 is persistently depressed in approximately 75%to 90%of MPGN
patients.
• C3 nephritic factor is found in 60% of cases of type II MPGN.
PROGNOSIS
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bad prognostic signs:at presentation include
the nephrotic syndrome,
renal insufficiency,
hypertension,
on renal biopsy, crescents
good long-term prognosis: asymptomatic hematuria
and proteinuria ,focal glomerular involvement on renal
biopsy.
Theraphy of MPGN
• The treatment of type I MPGN is based on the underlying
cause of the disease process. MPGN associated with
cryoglobulinemia and hepatitis C should be aimed at
treating hepatitis C virus infection (interferon/ribavirin),
• The treatment of MPGN associated with lupus or with
scleroderma should be based on the principles of care of
those rheumatologic conditions.
• Most recommendations for the treatment of idiopathic
type I MPGN are limited to studies in children where lowdose prednisone therapy improves renal survival.
New immunsuppresive regiments
• mycophenolate mofetil + corticosteroids
(5 grams/day at baseline to 2 and 2.6 grams/24 hours at
12 and 18 months),
Original Article
Mycophenolate mofetil treatment for therapy-resistant
glomerulopathies
SAHIN GM, SAHIN S, KANTARCI G.
NEPHROLOGY 2007; 12, 285–288
GLOMERULAR DISEASES THAT CAUSE
NEPHRITIC SYNDROME
IgA nephropathy (IgAN)
• Most common lesion found to cause primary
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glomerulonephritis throughout most developed countries of
the world.
IgA nephropathy common among Asians and Caucasians,
2:1 male to female predominance.
The etiology of IgA nephropathy is unknown, but infections
and/or genetic characteristics may predispose to the
development of kidney disease.
IgA nephropathy is often suspected on the basis of the
clinical history, but can be confirmed only by kidney
biopsy.
Clinical findings
Most patients with IgAN present with
• gross hematuria (single or recurrent), usually following
an upper respiratory infection (40–50%)
• microscopic hematuria with or without mild proteinuria
incidentally detected on a routine examination. (40%)
• Nephritic syndrome (10%)
• Malignant hypertension (<5%)
• Rarely, patients may develop AKI with or without
oliguria, due either to crescentic IgAN, or to gross
hematuria causing tubular occlusion and/or damage by
red cells.
Clinical features of IgAN
• Episodes of macroscopic hematuria tend to occur
with a close temporal relationship to upper
respiratory infection,including tonsillitis or
pharyngitis.
• The timing differs from that for PSGN, which has
an interval period of 7 to 14 days between the
onset of infection and overt hematuria.
Clinical features of IgAN
• Systemic symptoms are frequently found,
including nonspecific symptoms such as malaise,
fatigue, muscle aches and pains, and fever.
• Microscopic hematuria and proteinuria persist
between episodes of macroscopic hematuria.
• Associated hypertension is common
Clinical features of IgAN
• Although IgA nephropathy was previously thought to carry
a relatively benign prognosis, it is estimated that renal
insufficiency may occur in 20% to 30% of patients within 2
decades of the original presentation.
• Renal failure typically follows a slowly progressive course,
 a minority of patients with IgA nephropathy
manifests a fulminant course resulting in a rapid
progression to end-stage renal disease.
IgA nephropathy may be the glomerular expression of a
systemic disease Henoch-Schönlein purpura
poor prognoctic features
• Sustained hypertension,
• Persistent proteinuria greater than 1 g/day,
• Impaired renal function,
• Nephrotic syndrome
Laboratory Findings of IgAN
• microscopic hematuria and dysmorphic erythrocytes
• Proteinuria majority of subjects have less than 1 g/day of
protein.
• There are no specific serologic or laboratory tests
diagnostic of IgA nephropathy or Henoch-Schönlein
purpura.
• Although serum IgA levels are elevated in up to 50% of
patients, the presence of elevated IgA in the circulation is
not specific for IgA nephropathy.
• Complement levels such as C3 and C4 are typically
normal
PATHOLOGY
immunofluorescence microscopy
• globular deposits of IgA (often accompanied by C3 and
IgG) in the mesangium and, to a lesser degree, along the
glomerular capillary wall.
large, globular mesangial IgA deposits
Treatment of IgAN
• ACE-I or ARB treatment (1B) in IgAN, use blood pressure
treatment goals of 130/80mmHg in patients with proteinuria
<1 g/day, and
125/75mmHg when initial proteinuria is >1 g/day
• Corticosteroids(2C)in IgAN patients with persistent
proteinuria>1 g/day, despite 3–6 months of optimized
supportive care (including ACE-I or ARBs and blood
pressure control), and GFR >50 ml/min per 1.73m2, receive
a 6-month course of corticosteroid therapy.
• Fish oil in treatment(2D)of IgAN with persistent proteinuria
>1 g/d, despite 3–6months of optimized supportive care
(including ACE-I or ARBs and blood pressure control).
Immunosuppressive agents (cyclophosphamide,
azathioprine, MMF, cyclosporine)
• We suggest not treating with corticosteroids combined
with cyclophosphamide or azathioprine in IgAN patients
(unless there is crescentic IgAN with rapidly deteriorating
kidney function (2D)
• We suggest not using immunosuppressive therapy in
patients with GFR <30 ml/min per 1.73m2 unless there
is crescentic IgAN with rapidly deteriorating kidney function
Glomerular Diseases Associated with
Infection
• GN may occur as a concequence of infections.
• Post strep. GN: Patients presenting with features of
acute GN recent infection of pharynx or skin with group A
b-hemolytic strep.
• Diagnosis is suggested by history and urinalysis and
confirmed by low complement. Prognosis is excellent.
Treatment is supportive
Acute poststreptococcal
glomerulonephritis (PSGN)
•
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affects primarily children, with peak incidence between the ages of 2
and 6 years.
It may occur as part of an epidemic or sporadic disease, and only
rarely do PSGN and rheumatic fever occur concomitantly.
A latent period is present (7–21 days) from the onset of pharyngitis to
that of nephritis.
The hematuria is microscopic in more than two thirds of cases.
Hypertension occurs in more than 75% of patients
The clinical manifestations of acute PSGN typically resolve in 1 to 2
weeks as the edema and hypertension disappear after diuresis.
Both the hematuria and proteinuria may persist for several months,
but are usually resolved within a year.
Laboratory findings
• presence of dysmorphic red blood cells or red
blood cell casts.
• Proteinuria is nearly always present, typically
in the subnephrotic range.
• Nephrotic-range proteinuria may occur in as many as
20% of patients and is more frequent in adults than in
children.
• Throat or skin cultures may reveal group A streptococci
• elevated ASO titer above 200 units may be found in 90%
of patients;
• CH50 and C3 are reduced
Diffuse proliferative GN
Treatment of acute PSGN
• Supportive
• Supportive therapy may require the use of loop diuretics
such as furosemide to ameliorate volume expansion and
hypertension
RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS
AND CRESCENTIC GLOMERULONEPHRITIS
• Immune Complex–Mediated Crescentic GN
(e.g., MPGN, PSGN, or IgA nephropathy)
• Anti–Glomerular Basement Membrane GN
• 10% to 20% of crescentic GN
• This disease is characterized by circulating antibodies to the GBM and
deposition of IgG or rarely IgA along the GBM. Anti-GBM disease occurs as a
renal-limited disease (anti-GBM glomerulonephritis) and as a pulmonary-renal
vasculitic syndrome (Goodpasture syndrome).
• Pauci-Immune Crescentic Glomerulonephritis
Renal and Systemic Vasculitis
Pauci-Immune Crescentic
Glomerulonephritis
• The characteristic feature of
pauci-immune crescentic
glomerulonephritis is a focal
necrotizing and crescentic
glomerulonephritis in association
with a circulating ANCA.
• Pauci-immune crescentic
glomerulonephritis is usually a
component of a systemic small
vessel vasculitis,
Segmental glomerular necrosis and crescent
formation in a patient with
ANCA–associated small vessel vasculitis. The
fibrinoid material is red.
The uninvolved segments appear normal.
ANCA-associated syndromes
• Microscopic polyangiitis
• Wegener granulomatosis
• Churg-Strauss syndrome
• The presence of arteritis in a biopsy specimen with pauci-
immune crescentic glomerulonephritis indicates that the
glomerulonephritis is a component of a more widespread
vasculitis, such as microscopic polyangiitis,
• Wegener granulomatosis,or the Churg-Strauss syndrome.
• The pathogenesis of pauci-immune crescentic
glomerulonephritis is currently not fully understood.
• Many patients have a circulating ANCA, it has not been
conclusively proved that ANCA are involved in the
pathogenesis of pauci-immune small vessel vasculitis or
glomerulonephritis.
Laboratory Findings
• Approximately 80% to 90% of patients with pauci-immune
necrotizing and crescentic glomerulonephritis will have a
circulating ANCA.
• By indirect fluorescence microscopy on alcohol fixed
neutrophils, ANCA yields two patterns of staining:
• perinuclear (P-ANCA)
• cytoplasmic (C-ANCA)
• 60-70 % patients with pauci-immune necrotizing
crescentic glomerulonephritis without clinical evidence of
Systemic vasculitis will have MPO-ANCA or P-ANCA,
• approximately 30% will have PR3-ANCA or C-ANCA.
• Urinalysis findings include hematuria with dysmorphic red
blood cells, with or without red blood cell casts, and
proteinuria.
• Serum creatinine usually is elevated at the time of
diagnosis and rising
• Serum complement component levels are typically within
normal limits.
Fibrillary immunotactoid glomerulopathy
• characterized by patterned deposits seen by electron
microscopy.
• Most renal pathologists distinguish fibrillary
glomerulonephritis from immunotactoid glomerulopathy
based on the presence of fibrils of approximately 20-nm
diameter in the former and larger 30- to 40-nm diameter
microtubular structures
• The etiology and pathogenesis of fibrillary
glomerulonephritis and immunotactoid glomerulopathy are
not known, but both conditions have been associated with
lymphoproliferative diseases.
Clinical features
• less than 1% of native renal biopsies.
• Patients typically present with a mixture of the nephrotic and
nephritic syndrome features.
• Proteinuria is typically in the nephrotic range.
• Renal insufficiency, hematuria, and hypertension are
common at the time of presentation.
• 40% to 50% of patients develop end-stage renal disease
within 6 years of presentation
Secondary Glomerular Diseases
- SLE
- Antiphospholipid antibody syndrome
- Polyarteritis nodosa
- Churg-Strauss syndrome
- Glomerular involvement in other vasculitides
(temporal arteritis,takayasu disease)
- Sjögren syndrome, sarcoidosis, amyloidosis,
monoclonal immunoglobulin deposition disease
Lupus nephritis
• Renal involvement is common in idiopathic systemic lupus
erythematosus (SLE).
• An abnormal urinalysis with or without an elevated
plasma creatinine is present in a large proportion of
patients at the time of diagnosis, and may eventually
develop in more than 75 % of cases.
EPIDEMIOLOGY
• The prevalence of clinically evident renal disease in
patients with SLE ranges from 40 to 75 percent.
• Most renal abnormalities emerge soon after diagnosis
(commonly within the first 6 to 36 months)
PATHOGENESIS
• The pattern of glomerular injury seen in systemic lupus
erythematosus (and in other immune complex-mediated
glomerular diseases) is primarily related to the site of
formation of the immune deposits, which are primarily
due to anti-DNA.
Treatment of LN
• Class I LN (minimal-mesangial LN)treated as dictated by the
extrarenal clinical manifestations of lupus. (2D)
• Class II LN (mesangial-proliferative LN) and proteinuria <1
g/d as dictated by the extrarenal clinical manifestations of
lupus. (2D)
• Class II LN with proteinuria >3 g/d be treated with
corticosteroids or CNIs as described for MCD (2D)
• Class III LN (focal LN) and class IV LN (diffuse LN)—initial
therapy initial therapy with corticosteroids (1A), combined
with either cyclophosphamide (1B) or MMF (1B).
• If patients have worsening LN (rising SCr, worsening
proteinuria) during the first 3 months of treatment, a change
be made to an alternative recommended initial therapy, or a
repeat kidney biopsy be performed to guide further
treatment. (2D)
Class III LN (focal LN) and class IV LN (diffuse LN)—
maintenance therapy
• after initial therapy is complete, patients with class III and IV
LN receive maintenance therapy with azathioprine (1.5–2.5
mg/kg/d) or MMF (1–2 g/d in divided doses), and low-dose
oralcorticosteroids (1B)
• CNIs with low-dose corticosteroids be used for maintenance
therapy in patients who are intolerant of MMF and
azathioprine. (2C)
• After complete remission is achieved, maintenance therapy
be continued for at least 1 year before consideration is given
to tapering the immunosuppression. (2D)
class V LN
• We recommend that patients with class V LN, normal
kidney function, and non–nephrotic-range proteinuria be
treated with antiproteinuric and antihypertensive
medications, and only receive corticosteroids and
immunosuppressives as dictated by the extrarenal
manifestations of systemic lupus. (2D)
• We suggest that patients with pure class V LN and
persistent nephrotic proteinuria be treated with
corticosteroids plus an additional immunosuppressive
agent: cyclophosphamide (2C), or CNI (2C), or MMF(2D),
or azathioprine (2D).
C1 q Nephropathy
• C1q nephropathy refers to a disorder in which mesangial
proliferation is associated with mesangial deposits on
electron microscopy and prominent C1q deposits on
immunofluorescence microscopy.
• C1q nephropathy has been thought to be a subgroup of
primary focal segmental glomerular sclerosis
• reports describe different symptoms, histopathologies,
therapeutic responses and prognoses, suggesting that C1q
nephropathy may be a combination of several disease groups
rather than a single disease entity.
• C1q nephropathy may be associated with either MCD, FSG,
or proliferative glomerulonephritis. Criteria: predominant
C1q deposits on immunofluorescence microscopy and
no clinical evidence of systemic lupus erythematosus.
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