Lupus in dialysis - PowerPoint Presentation

Slide1

Lupus in dialysis

Dr : Mohamed Abdelhafez Nephrology specialist MNGHSlide2

Agenda

DEFINITION AND EPIDEMIOLOGYETIOLOGY AND PATHOGENESISRENAL AND EXTRARENAL MANIFESTATIONSIMMUNOLOGIC TESTS IN LUPUS NEPHRITISPATHOLOGY OF LUPUS NEPHRITIS

Lupus in Diaysis

MANGMENT OF LUPUS NEPHRITISSlide3

Definition

The American College of Rheumatology(ACR) criteria for the diagnosis of SLE have been widely used in both epidemiologic and treatment studies However , many patients with “lupus-like” conditions and others who meet fewer than four ACR criteria should still be recognized as requiring therapy.Lupus nephritis (LN) is an immune complex glomerulonephritis that is a common and serious feature of SLE .Slide4
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EPIDEMIOLOGY

The incidence and prevalence of lupus and LN are influenced by age,gender, ethnicity, geographic region, but across populations, clinically important kidney disease will occur in 40% of patients. The peak incidence of lupus is age 15 to 45 years, with women to men by 10 : 1.Among lupus patients, LN

affects both genders equally and is more severe in children and men.

Both lupus and LN are

three to four

times

more

common in blacks, Asians, and Hispanics than in Caucasians.

Additional risk factors for LN include younger age,

lower socioeconomic status

, more ACR criteria for SLE, longer disease

duration, family

history of

SLE

.Slide6

Agenda

DEFINITION AND EPIDEMIOLOGYETIOLOGY AND PATHOGENESISRENAL AND EXTRARENAL MANIFESTATIONSIMMUNOLOGIC TESTS IN LUPUS NEPHRITISDIFFERENTIAL DIAGNOSIS

PATHOLOGY OF LUPUS NEPHRITISMANGMENT OF LUPUS NEPHRITISSlide7

ETIOLOGY

Multiple genes predispose to lupus, supported by 1 clustering in families, 2 concordance of SLE in more than 25% of identical twins ,3 frequency of positive autoantibodies and autoimmune disorders in family of SLE patients

.Homozygous deficiency of complement components (

C1q, C2, C4

) carries a

high risk

for development of

SLE

Hormonal

factors

are

suggested by

the strong female predisposition, the exacerbations during

or shortly

after

pregnancy.

Whereas exposure to

certain

medications

can

produce SLE or a lupus-like

syndrome .Slide8

PATHOGENESIS

A number of mechanisms may contribute to SLE, including abnormal exposure to self antigens, T cell hyperactivity , increased B cell–stimulating cytokines, and B cell hyperactivity.The failure of apoptotic mechanisms to delete or to silence autoreactive cells (tolerance) may allow clonal expansion of such cells later in life, leading to autoantibody production

.Autoantibodies combine with antigen to produce immune complexes that if

not adequately

cleared may deposit in various organs, inciting

inflammatory responses.

Complement components

activated by

immune complexes and contribute to the inflammatory cascade.

A hallmark of glomerular involvement in LN is the accumulation of

immune

complexes.

Patients

with LN have autoantibodies

against double-stranded

DNA (

dsDNA

),

Sm

antigen, C1q,

nucleosomes, and

other

antigens .Slide9

PATHOGENESIS

Mesangial and subendothelial immune deposits are derived from deposition of circulating immune complexes, whereas subepithelial immune complexes may include those formed in situ.Activation of procoagulant

factors, leukocyte infiltration into the kidneys with release of their proteolytic enzymes, and activation of cytokines associated with cellular proliferation and matrix formation.Slide10

Agenda

DEFINITION AND EPIDEMIOLOGYETIOLOGY AND PATHOGENESISRENAL AND EXTRARENAL MANIFESTATIONSIMMUNOLOGIC TESTS IN LUPUS NEPHRITISDIFFERENTIAL DIAGNOSIS

PATHOLOGY OF LUPUS NEPHRITISMANGMENT OF LUPUS NEPHRITISSlide11

CLINICAL

MANIFESTATIONSRenal ManifestationsSlide12

CLINICAL

MANIFESTATIONSExtrarenal ManifestationsPatients with active SLE often present with nonspecific complaints of malaise, low-grade fever, poor appetite, and weight lossOther common features include patchy alopecia; oral or nasal ulcerations;

arthralgias and nondeforming arthritis.

A

variety of dermal findings

,

photosensitivity, Raynaud’s phenomenon, and

“butterfly” facial rash.

Livedo

reticularis

is seen

in 15% of

cases and may be associated with miscarriages,

thrombocytopenia.Slide13

Neuropsychiatric

involvement presents with headache,nerve palsies, frank coma, and psychoses. Serositis, in the form of pleuritis or pericarditis, affects up to 40% of patients. Pulmonary hypertension can develop silently as a result of multiple pulmonary emboli or intravascular coagulation in association with APA. Libman-Sacks endocarditis

and more common mitral valve prolapse can be detected clinically or by echocardiography.

Hematologic abnormalities

include anemia

caused by

impaired erythropoiesis, autoimmune hemolysis, and bleeding.

Thrombocytopenia and leukopenia may be part of the

disease or

may result from complications of therapy

.

Thrombotic events

should prompt a search for

APA

and other

procoagulant

abnormalitiesSlide14

Agenda

DEFINITION AND EPIDEMIOLOGYETIOLOGY AND PATHOGENESISRENAL AND EXTRARENAL MANIFESTATIONSIMMUNOLOGIC TESTS IN LUPUS NEPHRITISDIFFERENTIAL DIAGNOSISPATHOLOGY OF LUPUS NEPHRITIS

MANGMENT OF LUPUS NEPHRITISSlide15

IMMUNOLOGIC TESTS IN LUPUS NEPHRITISSlide16

Agenda

DEFINITION AND EPIDEMIOLOGYETIOLOGY AND PATHOGENESISRENAL AND EXTRARENAL MANIFESTATIONSIMMUNOLOGIC TESTS IN LUPUS NEPHRITISPATHOLOGY OF LUPUS NEPHRITISMANGMENT OF LUPUS NEPHRITISSlide17

Agenda

DEFINITION AND EPIDEMIOLOGYETIOLOGY AND PATHOGENESISRENAL AND EXTRARENAL MANIFESTATIONSIMMUNOLOGIC TESTS IN LUPUS NEPHRITISPATHOLOGY OF LUPUS NEPHRITISMANGMENT OF LUPUS NEPHRITISSlide18

PATHOLOGYAlthough LN may affect all structures of the kidney, glomerular involvement has been the best studied component and correlates well with the presentation, course, and treatment.The currently used International Society of Nephrology (ISN)/Renal Pathology Society (

RPS) classificationThere is a deficit of the

ISN/RPS

system

,

as

ahistologic

and clinical involvement of other renal compartments

is seen,

because interstitial and

vascular injury

are predictors

of kidney outcomes.Slide19

Transformation of

pathologySerial biopsy specimens often show transformation from one to another histologic glomerular class.Some patients with increased clinical activity will transform from a more benign or less proliferativeclass

(ISN class II or V) to a more active proliferative lesion (ISN class III or IV).

With successful treatment, other

patients will

transform from a proliferative class (ISN class III or IV) to

a more

predominant membranous pattern (ISN class V

).

Extremely uncommon are patients who have active

proliferative LN

on biopsy but no clinical or urinary sediment

changes,

with normal anti-

dsDNA

and serum

complement levels

, so-called

silent LN

. Slide20

PATHOLOGYSlide21

ISN/RPS

class I: minimal mesangial lupus nephritis. Light microscopy is normal, but immunoperoxidase shows C1q localization (associated with IgG and C3) throughout the mesangial area.Slide22

ISN/RPS class II: lupus nephritis (mesangial disease).

A, Mesangial expansion but little increase in tuft cellularity, and the peripheral capillary walls are normal. (Silver methenamine stain.) B, Extensive mesangial IgG deposits shown by immunoperoxidase; the aggregates are just beginning to invade peripheral capillary walls.Slide23

SN/RPS class III: focal proliferative lupus nephritis.

A, Low-power magnification shows focal and segmental proliferative lesion–active (class IIIA) with less than 50% of glomeruli affected. (Hematoxylineosin stain.) B, Area of focal necrosis containing cellular debris,karyorrhexis (arrow), is surrounded by an area of cellular proliferation. (Silver methenamine/HE.)Slide24

ISN/RPS class IV: lupus nephritis.

A, Active, diffuse proliferative lupus nephritis. B, Immunoperoxidase staining shows dense, irregular aggregates of IgG along the peripheral capillary walls.Slide25

ISN/RPS class V: membranous lupus.

B, Silver methenamine–stained section shows some double contouring of the silver-positive basement membrane (arrow) and subendothelium-deposited material as well as the characteristic silver-positive spikes of basement membrane–like material. C, Electron micrograph shows the predominantly subepithelial electrondensedeposits (D) separated by protrusions of basement membrane material (spikes, S)Slide26

Interstitial lupus

nephritis A, Interstitial infiltrate invading and destroying tubules (tubulitis). Tubular basement membranes, which stain black with silver, are digested in the areas of tubulitis (arrow). B, Immunofluorescence shows aggregates of C3 in the tubular basement membrane

(right) as well as within the glomerulus (left).

Such

tubular basement membrane aggregates are common in lupus

nephritisSlide27

Vascular damage in lupus nephritis.

Thrombus (arrow) occludes a glomerular capillary loop in this class IV biopsy . A thrombus contains platelets and fibrin as well as immunoglobulins and thus has some characteristics of true thrombus. (Silvermethenamine

/hematoxylin stain.)Slide28

Clinical and

Histopathologic CorrelationsPatients with ISN class I biopsies usually have no evidence of clinical renal disease. patients with ISN class II may have elevated anti-dsDNA or low complement levels, but in general, their urinary sediment

is inactive, hypertension is infrequent, the GFR is preserved, and proteinuria is rarely above 1 g/24 h.

Patients with

class I

and class II biopsy findings have an excellent renal prognosis

unless they

transform to another pattern.

However

, patients with LN (

especially classes

I and II) may be more susceptible to

non–immune complex

podocyte

injury (

lupus

podocytopathy

) that shows a

histologic pattern

of minimal change disease (MCD) or focal

segmental

glomerulosclerosis

(FSGN), and is often accompanied by

nephrotic

range proteinuria.Slide29

Patients with active ISN class IIIA or IIIA/C often have

microhematuria, hypertension, low complement levels, and proteinuria.From one fourth to one third of patients will have the nephrotic syndrome, and up to one in four will have an elevated serum creatinine .Patients with focal glomerular scarring (ISN class IIIC) usually have hypertension and reduced renal function but without active urinary sediment. Patients

with mild proliferation in only a few glomeruli generally respond well to therapy, with less than 5% progressing to renal failure during 5 years of follow-up

Others with more glomerular involvement or

with necrotizing

features and crescent formation have a prognosis

similar to

that of class IVA patients.Slide30

Patients with ISN class

IVA have high serologic activity (low serum complement and high antidsDNA) with active urinary sediment, hypertension, heavy proteinuria, and reduced GFR. Class IV diffuse proliferative disease carries

the worst renal prognosis in most

series.

Advanced sclerotic

LN

class

VI

, is usually the result

of “burnt-out

” class III or class IV LN. Slide31

Patients with ISN class

V typically present with proteinuria and features of the nephrotic syndrome. At biopsy, however, up to 40% will have subnephrotic proteinuria, and up to 20% will have less than 1 g/24 h of proteinuria. Patients with ISN class V typically have

less clinical renal and serologic activity. Nephrotic ISN class V patients are

predisposed to

thrombotic complications, such as renal vein

thrombosis and

pulmonary emboli

.

Ten-year renal survival rates are 75%

to 85

%.Slide32

Histologic

Prognostic FactorsFeatures of reversible (active) or irreversible (chronic) damage on biopsy may be able to predict the course of LN patients. The higher activity index or chronicity index are more likely to progress to renal failure. The

renal prognosis is poor if biopsy specimens show extensive glomerulosclerosis or interstitial fibrosis.

Patients

with high

degrees of

both activity and chronicity on biopsy (activity index >7

plus chronicity

index >3) fare

poorly

.Slide33
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SURVIVAL

Fifty years ago, few patients with severe LN survived more than a few years, and half of those with even less severe forms of LN died within 5 years. Most patients now have a response to early treatment, followed by relatively quiescent disease under continuing immunosuppression that eventually can be taperedSome patients will continue to have no disease activity;

others will relapse with time. The frequency of relapse depends not only

on the underlying disease severity, but also on the intensity

and duration

of continued immunosuppression.Slide35

End-stage renal disease (ESRD) now affects 8% to 15% of patients with

LN.A renal biopsy is often useful to determine whether the disease is still active and potentially treatable or all chronic and irreversibly scarred.In patients with active LN, fatal infections, are the most common cause of death. Studies confirm that almost half of all lupus deaths are the result of excess cardiovascular mortality, particularly from premature myocardial ischemia.Epidemiologic predictors include race, with blacks and Hispanics having worse outcomes.Male gender, younger age (<24 years), and lower socioeconomic statusare associated with a worse renal outcome.Slide36
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Agenda

DEFINITION AND EPIDEMIOLOGYETIOLOGY AND PATHOGENESISRENAL AND EXTRARENAL MANIFESTATIONSDIFFERENTIAL DIAGNOSISIMMUNOLOGIC TESTS IN LUPUS NEPHRITISPATHOLOGY OF LUPUS NEPHRITISSlide42

The ISN/RPS biopsy classification should guide initial

therapy. patients assigned to ISN class I and class II need No therapy directed at the kidney. The majority will have a benign long-term kidney outcome . An exception is the group of lupus patients with lupus podocyte

injury, who often respond to a short course of high-dose corticosteroids similar to patients

with MCD or FSGN

.Slide43
Slide44
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TREATMENTSlide46

LN AND

RENAL TRANSPLANTATIONLupus represents only 1% to 2% of patients with ESRD.Extrarenal lupus will be inactive inpatients by the time they reach ESRD, but some may still have active extrarenal disease that requires immunosuppression while receiving renal replacement therapy.Most centers delay transplantation until lupus activity is quiescent for 6 months.

For patients who are clinically inactive but retain serologic activity with elevated anti-DNA antibody levels, starting

transplant

immunosuppressives

prophylactically several

weeks to 1 month before living donor

transplantation may

suppress the serologic

activity

.Slide47

Allograft thrombosis(arterial , venous , or

intraglomerular) may occur after transplantation, especially in patients with APA. APA-positive patients with a prior thrombotic event should be anticoagulated shortly after transplantation. Outcomes in SLE patients undergoing transplantation are similar to those of patients with other diseases.Recurrent LN occurs in 2% to 11% of transplanted kidneys .Graft Loss in recurrent disease : rare .Slide48

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