Download clinical features of adult irgn

Dr.Mousavi
Postinfectious glomerulonephritis (PIGN) is an immunemediated
glomerulonephritis caused by nonrenal bacterial infections.
In the past, most cases occurred in childhood and followed
streptococcal upper respiratory tract or skin infections, and hence
were called ‘post-streptococcal glomerulonephritis(PSGN).
The past 3 decades have witnessed amajor shift in epidemiology
and outcome.
Because infection is usually ongoing at the time GN is diagnosed,
the term infection-related glomerulonephritis(IRGN) has been
proposed.
In developed countries in the modern era, a significant proportion
of cases afflict adults, particularly the elderly or
immunocompromised.
EPIDEMIOLOGY OF ADULT IRGN
The incidence of IRGN in children and adults in both the
industrialized and developing countries has decreased over the past
5 decades.
This trend is likely due to improvement in living conditions, early
and effective use of antibiotics, and the increasing practice of
water fluorination, which
attenuates
the expression of
Streptococcus pyogenes virulence Factors.
Postinfectious GN can occur at any age but usually develops in
children. Most cases occur in patients aged 5-15 years; only 10%
occur in patients older than 40 years.
There has been also a recent change in the age predominance in
IRGN. In studies reported 4 decades ago,<6% of affected adults
were elderly, compared with 34% in a recent report.
This shift is likely due to improved life expectancy, higher
frequency and severity of infections in the elderly population,
and higher prevalence of diabetes.
The global burden of IRGN in adults was 68,000 per year. The true
incidence is likely much higher as epidemiologic studies included
only symptomatic patients, and it is known that subclinical IRGN
is at least four times more common than clinically evident
disease.
All reported series of adult IRGN after 1990, found a male
predominance, with male:female ratio ranging from 1.4:1 to 3:1
Most reported patients were Caucasians and Asians, although
Blacks, Hispanics, and Native Americans can be affected.
Etiology
The spectrum of causative pathogens and the sites and
duration of infection differ in adults compared with children.
In adults, staphylococcal infections are now as common as
streptococcal infections and are 3-fold more common in the
Elderly.
In contrast to children in whom the latent period between
infection and onset of renal disease is typically 1–6 weeks, in a
significant percentage of adults and particularly elderly patients the
infection is only discovered at the time of IRGN diagnosis.
In one study of adult IRGN, 2/3of patients with staphylococcal
infection were diabetics compared to only 8% with streptococcal
infection.
Themajority of cases of Staphylococcus-related GN are caused by
Staphylococcus (S) aureus, with higher incidence of
methicillin-resistant S. aureus (MRSA) than methicillin sensitive
S. aureus, although rarely the disease can be
caused by coagulase-negative Staphylococcus including
S. epidermidis and S. hemolyticus.
S. epidermidis is the leading pathogen in shunt nephritis.
Cytomegalovirus (CMV), coxsackievirus, Epstein-Barr virus (EBV),
hepatitis B virus (HBV), rubella, rickettsiae (as in scrub typhus), and
mumps virus are accepted as viral causes only if it can be
documented that a recent group A beta-hemolytic streptococcal
infection did not occur. Acute GN has been documented as a rare
complication of hepatitis A.
Attributing glomerulonephritis to a parasitic or fungal etiology
requires the exclusion of a streptococcal infection. Identified
organisms include :
Coccidioides immitis and the following parasites Plasmodium
malariae, Plasmodium falciparum, Schistosoma mansoni,
Toxoplasma gondii, filariasis, trichinosis, and trypanosomes
Risk factor & Site of infection
An immunocompromised background is present inover a half of
adult cases in developed countries.
Diabetes isa major risk factor in the United States, particularly in
the elderly population, in whom it was present in 49% of patients
in one study.
Alcoholism is another common predisposing condition,
particularly in Europe.
Other less frequent risk factors are malignancy (most commonly
carcinoma), severe malnutrition, synthetic heart valve,
intravenous drug use, AIDS, and tuberculosis.
The teeth and gums were a common site of infection in two series of
adult IRGN from Europe, in which asignificant percentage of patients
were alcoholics with or without cirrhosis. Poor oral hygiene and
tooth decay in alcoholics make them particularly prone to dental
bacterial infections and IRGN.
In some adults with IRGN, there is more than one site of
infection, and the cultures grow more than one bacterium.
Of note, in a minority of adult cases, the infection is not clinically
evident,and some patients with clinically evident infection may
have negative cultures, especially following antibiotics.
pathogenesis
This could occur by a number of different mechanisms:
(1) by introduction of an antigen into the glomerulus (planted
antigen)
(2) by the deposition ofcirculating immune complexes
(3) by alteration of a normalrenal antigen that causes it to
become a self-antigen
(4)by induction of an autoimmune response to a self-antigen
byway of antigenic mimicry.
It is conceivable that more than one streptococcal antigen may
be involved in the pathogenesis of acute PSGN, and more than
one pathogenic mechanism may be at play simultaneously.
The fact that IRGN can be caused by so many different bacteria
but develops in only a minority of infected patients argues for
critical host factors in disease susceptibility. There is some
evidence for a genetic predisposition to IRGN.
recent study found asignificantly higher frequency of HLADRB1*03011 allele in Egyptian children with PSGN compared
with controls.Other studies found an association with HLADPA1*01,DPA1*0201 and HLA-DRW4.
A defect in the regulating mechanisms of the alternative
pathway of complement has been suggested for patients with
persistent IRGN.
CLINICAL FEATURES OF ADULT IRGN
The clinical renal manifestations of acute adult IRGN bear some
similarities to and notable differences from childhood IRGN. In both
age groups, symptomatic patients most commonly manifest acute
nephritic syndrome, with new onset hematuria and proteinuria,
edema, hypertension, and reduced renal function.
Hypertension is present in 60–84% of adult patients at
presentation, and is more frequent in the elderly. In one study in
the elderly, new-onset or longstanding hypertension was present in
12% and 72% of cases,
seizures may herald the development of severe hypertension and
fluid overload in childhood IRGN, they are not a typical feature of
adult IRGN.
Encephalopathy presenting as confusion, headache,
somnolence,or even convulsion is not common and may affect
children more frequently than adults. The encephalopathy is not
always attributable to severe hypertension, but may be the result
of central nervous system vasculitis instead.
Peripheral edema occurs in 2/3 of adult patients, because of
water and sodium retention.
The edema typically appears in the face and upper extremities.
Ascites and anasarca may occur in children.
Anuria is infrequent, however, and if persistent may indicate the
development of crescentic glomerulonephritis.
New-onset or exacerbated heart failure is not uncommon in
elderly patients with IRGN and is attributable to the higher
prevalence of underlying cardiovascular disease and decreased
ability to handle the salt and water retention associated with
glomerulonephritis.
Aside from congestive heart failure, extrarenal manifestations
rarely occur in adults with IRGN. Interestingly, purpura was
present in 18% of adult patients with IRGN.
IgA-dominant Staphylococcus-related GN also rarely has a
Henoch–Scho¨nlein purpura (HSP)–like presentation,
including lower extremity purpuric rash.
Patients with shunt nephritis, who are usually children and
only rarely adults, frequently have recurrent fever, anemia,
hepatosplenomegaly, and cerebral symptoms.
The degree of proteinuria varies from o1 to>3 g/day, with a
quarter to a third of patients having full nephrotic syndrome.
Almost all patients have microhematuria, with or without red
blood cell casts, and gross hematuria occurs in 17–56% of patients.
Subclinical microscopic hematuria may be four times more
common than overt acute PSGN
The hematuria is microscopic in more than two thirds
of cases. Patients presenting with macroscopic anemia commonly
report gross hematuria and transient oliguria.
Leukocyturia is frequent, reported in 58–65% of patients
Serum creatinine at presentation is elevated in the vast majority
of patients, and it is higher in elderly patients than younger
adults, and higher in those with underlying diabetic
Glomerulosclerosis. In one study, 67% of elderly patients
(>64 years) had a peak serum creatinine >4 mg/dl as
compared with 32% in younger adults (16–64 years),(P=0.03).
In contrast to children in whom the need for dialysis for severe
acute renal failure is uncommon, close to a half of elderly patients
require acute dialysis for uremic symptoms and/or fluid overload.
Hypocomplementemia is present in 35–80% of adults with
IRGN, compared with about 90% of children.
In most patients, C3 is depressed with or without depression of
C4.
Usually, serum complement levels normalize within 2 months of
Presentation, except in those with persistent infection.
Patients with shunt nephritis frequently have positive serum
cryoglobulin, positive antinuclear antibody, circulating
immune complexes (ICs), elevated serum IgM or IgG
levels, and elevated erythrocyte sedimentation rate.
Aside from patients with shunt nephritis or infectious
endocarditis-associated GN, the vast majority of adults with
IRGN have negative testing for cryoglobulin.
with the exception of a reported case of IgA-dominant IRGN due to
staphylococcal line infection Anti-neutrophil cytoplasmic
antibody (ANCA) seropositivity (directed against MPO or
PR3) occurs in 8% of elderly patients with IRGN overall and
in 25% of patients with infectious endocarditis–associated
GN, where it may contribute to the development of the
characteristic diffuse crescentic and necrotizing GN.
Therefore, ANCA testing is recommended in all patients with
infectious endocarditis–associated GN and in any patient with IRGN
whose biopsy shows diffuse crescents and/or any lesion of fibrinoid
necrosis to rule out concurrent ANCA-mediated disease. Conversely,
infectious endocarditis should be excluded in patients
presumed to have ANCA-associated glomerulonephritis
because of the attendant risks of immunosuppression.
prognostic factors
The independent poor prognostic factors in adult IRGN
include:
 older age
 higher serumCreatinine at biopsy
 more tubulointestinal scarring
the presence of underlying conditions
 Diffuse crescent formation
Proteinuria may persist for 6 months and microscopic hematuria
for up to 1 year after onset of nephritis.
Approximately 15% of patients at 3 years and 2% of patients at 710 years may have persistent mild proteinuria. Long-term
prognosis is not necessarily benign.
Some patients may develop hypertension, proteinuria, and renal
insufficiency as long as 10-40 years after the initial illness.
In contrast to childhood PSGN and epidemic PSGN, which usually
resolve, sporadic adult IRGN has a guarded prognosis, with a
significant proportion developing chronic kidney disease or endstage renal disease (ESRD).
TREATMENT AND OUTCOME
The treatment of adult IRGN should include eradication of infection
and management of complications of nephritis.
Hospital admission may be necessary, particularly in elderly patients
who are vulnerable to complications such as congestive heart failure.
Active infection should be eradicated with antibiotics and, if needed,
with surgery.
Treatment of acute nephritic syndrome includes
antihypertensivedrugs, diuretics, and dietary salt restriction.
In patients with persistent moderate or heavy proteinuria, renin–
angiotensin system blockade is recommended to slow disease
progression.
The role of immunosuppressive therapy in the treatment of
sporadic bacterial IRGN in adults has not been tested in a
randomized prospective clinical trial; the available data are based
on observations from retrospective studies. Despite the frequent
use of steroids for the treatment of adult IRGN (used in 22–48% of
patients in various studies for renal insufficiency with or without
crescentic disease), none of the studies in which statistical analysis
was performed found a beneficial effect of steroids on outcome.
In adult patients with diffuse crescentic and necrotizing IRGN
(particularly those with positive ANCA titers), a course of pulse
steroids with or without cyclophosphamide can be offered (based
on extrapolation from other etiologies of rapidly progressive
glomerulonephritis), provided that there is no active infection or
contraindication related to the immunocompromised state. The
addition of steroids is unlikely to be harmful in PSGN, but for other
IRGN the risks of using steroids should be carefully balanced against
potential benefits.
creatinine
Pulse Methyl P
4.5
4
3.5
3
Plasma exchange +IVIG
2.5
2
1.5
1
0.5
0
Kidney
Biopsy
creatinine
blood flow:
10o-150cc/min
30-50cc/min
Plasma
removal
30-50cc/min
Plasma exchange*6 •
IVIG(2gr/kg) •
94/11/27
4/1
94/11/28
3/5
94/11/29
3/3
94/11/30
3
94/12/1
2.8
94/12/2
2/4
94/12/3
2/2
Plasma exchange
Thrombocytopenia
Fever
Seizure
DATE
PLT
94/12/2
109000
94/12/3
73000
94/12/4
33000
94/12/5
28000
94/12/7
33000
94/12/8
30000
Sepsis workup
U/C: Negative
B/C: Negative
ESR:3
CRP: -
AB: Vancomycin
Neurological consult(Tonic clonic seizure)
Phenytoin
Brain CT/brain MRI(R/O CNS vasculitis)
EEG
Dopler sonography carotid artery
Brain CT/MRI:No significant leision
EEG:No epileptic discharge
Dopler sonography carotid artery :Normal
Hematologycal consult
BMA&BMB:Normal
PBS:Hypochrome:1+
Anisocytosis:1+
Schistocyte:RARE
Retic:0.5%
LDH:557
Echocardiography(Ruled out endocarditis)
cardiac systolic & diastolic function was
normal without any valvular disease. No
vegetation
creatinine
Pulse Methyl P
4.5
4
3.5
3
Plasma exchange +IVIG
2.5
2
1.5
1
0.5
0
Kidney
Biopsy
creatinine
Thank you very much
for your attention
The End