Acute Postinfectious Glomerulonephritis

in the Modern Era

Experience With 86 Adults and Review of the Literature
Samih H. Nasr, MD, Glen S. Markowitz, MD, Michael B. Stokes, MD, Samar M. Said, MD,
Anthony M. Valeri, MD, and Vivette D. DAgati, MD
Abstract: Acute postinfectious glomerulonephritis (APIGN) is
uncommon in adults, and its incidence is progressively declining in
developed countries. To our knowledge there are no modern North
American series addressing epidemiology and outcome. Here we
report the clinical and pathologic findings in 86 cases of adult
APIGN diagnosed by renal biopsy in a large New York referral
center between 1995 and 2005. The male:female ratio was 2:1, and
mean age was 56 years, with 33.7% aged older than 64 years. Of the
patients, 38.4% had an immunocompromised background, including
diabetes (29.1%), malignancy (4.7%), alcoholism (2.3%), acquired
immunodeficiency syndrome (AIDS) (2.3%), and intravenous drug
use (1.2%). The most common sites of infection were upper
respiratory tract (23.3%), skin (17.4%), lung (17.4%), and heart/
endocarditis (11.6%). The 2 most frequently identified infectious
agents were streptococcus (27.9%) and staphylococcus (24.4%).
Hypocomplementemia was present in 73.9% of patients. The most
common histologic patterns were diffuse (72.1%), focal (12.8%),
and mesangial (8.1%) proliferative glomerulonephritis.
Outcome analysis was performed on the 52 patients with a
follow-up of
3 months (mean, 25 mo). Among the 41 patients
without underlying diabetic glomerulosclerosis, 23 (56.1%)
achieved complete remission, 11 (26.8%) had persistent renal
dysfunction, and 7 (17.1%) progressed to end-stage renal disease
(ESRD). Of the 11 patients with underlying diabetic glomerulosclerosis, 2 (18.2%) had persistent renal dysfunction, and the
remaining 9 (81.8%) progressed to ESRD (p < 0.001). In patients
without underlying diabetic glomerulosclerosis, correlates of
complete remission were younger age, female sex, lower serum
creatinine at biopsy, and absence of immunocompromised state. By
multivariate analysis, age and serum creatinine at biopsy inversely
correlated with complete remission, and serum creatinine at biopsy
was the only correlate with ESRD. Outcome did not correlate with
any pathologic feature (including crescents) or steroid treatment.

From Department of Pathology (SHN, GSM, MBS, SMS, VDD) and

Department of Medicine, Division of Nephrology (AMV), Columbia
University, College of Physicians & Surgeons, New York, New York.
This study was presented orally as an abstract at the annual meeting of the
American Society of Nephrology, October 31November 5, 2007, San
Francisco, CA.
Address reprint requests to: Samih H. Nasr, MD, Department of Pathology,
Columbia University, College of Physicians & Surgeons, 630 West
168th Street, VC14-224, New York, NY 10032. Fax: 212-342-5380;
e-mail: sn386@columbia.edu.
Copyright n 2008 by Lippincott Williams & Wilkins
ISSN: 0025-7974/08/8701-0021
DOI: 10.1097/MD.0b013e318161b0fc

Diabetes and aging have emerged as major risk factors for

adult APIGN. Full recovery of renal function can be expected in just
over half of patients, and prognosis is dismal in those with
underlying diabetic glomerulosclerosis.
(Medicine 2008;87:2132)
Abbreviations: APIGN = acute postinfectious glomerulonephritis, C =
serum complement, DGS = diabetic glomerulosclerosis, EM = electron
microscopy, ESRD = end-stage renal disease, GN = glomerulonephritis,
H & E = hematoxylin and eosin stain, IF = immunofluorescence,
IVDU = intravenous drug use, LM = light microscopy, MPGN =
membranoproliferative glomerulonephritis, URT = upper respiratory tract.

INTRODUCTION

cute postinfectious glomerulonephritis (APIGN) most

frequently affects children and is relatively uncommon
in adults. The disease incidence has declined sharply in
industrialized countries over the last 50 years. In the past, the
vast majority of cases followed streptococcal infections,
typically involving the upper respiratory tract (URT) or skin.
In recent years, non-streptococcal infections, particularly
staphylococcal and Gram-negative infections, have become
more frequent precipitants of adult APIGN28. Adults with
an immunocompromised background, especially due to alcoholism, are at higher risk for developing the disease21,28. Most
children with APIGN recover completely, but there is general
agreement that the prognosis is more guarded in adults. While
several large studies performed before 1980 evaluated the
course of nonepidemic adult APIGN4,18,22,23,26, there have been
few reports in the modern era, and, to our knowledge, none has
addressed the North American experience21,28,29. Furthermore,
there are limited published data regarding the clinicopathologic
findings and outcome in the subset of adults with APIGN who
have underlying diabetic glomerulosclerosis (DGS), even
though APIGN is one of the most common nondiabetic
glomerular diseases to occur in diabetics16,25,27,30,50,56.
In the current report we retrospectively examined 86
adult cases of APIGN diagnosed on renal biopsy at a large
New York referral center from 1995 to 2005, including 16
with histologic evidence of DGS. The demographic, clinical,
pathologic, and outcome data define an evolving spectrum of
adult APIGN in the new millennium.

METHODS
All native renal biopsies received and processed at
Columbia University Medical Center from 1995 to 2005

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21

Medicine  Volume 87, Number 1, January 2008

Nasr et al

(n = 14,138) were reviewed retrospectively for the diagnosis of APIGN in adults (aged
16 yr of age). Ninety-two
cases were identified, indicating a biopsy incidence of
0.6%. The diagnosis of APIGN was established by clinicopathologic correlation. For the purpose of this study, at
least 3 of the following 5 criteria were required for study
entry:
1) clinical or laboratory evidence of infection preceding
the onset of glomerulonephritis (GN);
2) depressed serum complement;
3) endocapillary proliferative and exudative GN on
light microscopy (LM);
4) C3-dominant or codominant glomerular staining on
immunofluorescence (IF); and
5) hump-shaped subepithelial deposits on electron
microscopy (EM).
Six cases of presumed APIGN were excluded because
they fulfilled only 2 of these criteria (including 4 with typical
humps on EM but no evidence of preceding infection and 1
with a membranoproliferative glomerulonephritis (MPGN)
pattern secondary to schistosomiasis). The remaining 86
cases fulfilled at least 3 criteria and form the basis of this
report. Among these, 32 cases fulfilled 5/5 criteria (37.2%),
35 fulfilled 4/5 criteria (40.7%), and 19 fulfilled 3/5 criteria
(22.1%).
Standard processing of renal biopsies included LM, IF,
and EM. For LM, all cases were stained with hematoxylin
and eosin, periodic acid-Schiff, Masson trichrome, and Jones
methenamine silver. For IF, 3-mm cryostat sections were
stained with polyclonal FITC-conjugated antibodies to IgG,
IgM, IgA, C3, C1q, kappa, lambda, fibrinogen, and albumin
(Dako Corp., Carpinteria, CA). EM was performed using a
JEOL 100s electron microscope.
Clinical data, including demographic information,
presenting clinical and laboratory findings, medical history,
treatment, and follow-up, were obtained from referral forms
submitted at the time of biopsy and from follow-up
telephone interviews with the referring nephrologist. The
following clinical definitions were used: nephrotic range
proteinuria,
3.0 g/d; hypoalbuminemia, serum albumin
<3.5 g/dL; renal insufficiency, serum creatinine >1.2 mg/dL;
nephrotic syndrome, nephrotic range proteinuria, hypoalbuminemia, and peripheral edema; and hypertension, systolic
blood pressure >140 mmHg, diastolic blood pressure >90
mmHg, or ongoing treatment with antihypertensive medications. For outcome analysis, complete remission was
defined as normalization of serum creatinine to baseline
levels or to a creatinine 1.2 mg/dL (for those patients in
whom baseline creatinines were unavailable); persistent
renal dysfunction was defined by elevation of serum
creatinine 0.2 mg/dL above baseline levels or follow-up
creatinine >1.2 mg/dL (for those in whom baseline levels
were unavailable); and end-stage renal disease (ESRD) was
defined as requiring renal replacement therapy.
Continuous variables are reported as mean SD.
Statistical analysis was performed using SPSS for Windows,
version 15.0 (SPSS, Chicago, IL). Analysis was performed
using exact statistical methods. Univariate analysis was

22

performed using the Mann-Whitney U test, the KruskalWallis test, and the Fischer exact test as appropriate for
variable type. Multivariate analysis was performed using
binary and multinomial logistic regression analysis. Statistical significance was assumed at p < 0.05.
The study was approved by the Institutional Review
Board of Columbia University Medical Center.

RESULTS
Clinical Features of Adult APIGN
The majority of patients were white (59.3%) and male
(66.3%) (Table 1). The mean age was 56 years, and one-third
of patients were older than 64 years. Of the patients, 38.4%
had an immunocompromised background, and the most
frequent predisposing factor for infection was diabetes
(present in 29.1% of patients). The site of infection was
identified in 83.7% of patients; the 4 most common sites
were URT (in 23.3% of patients), skin (17.4%), lung
(17.4%), and heart/endocarditis (11.6%) (Table 2). The
infectious agent was identified in 58.1% of patients (by
positive culture in the case of nonstreptococcal infection and
by positive culture, elevated anti-streptolysin O antibody, or
anti-DNase B antibody in the case of streptococcal infection)
(see Table 2). Streptococcus and staphylococcus were by far
the 2 most frequent causative agents, found in 27.9% and
24.4% of patients, respectively. URT was the most frequent
site of streptococcal infection (46%), while the skin was the
most common site of staphylococcal infection (38%). Twothirds of patients with staphylococcal infections were
diabetic compared with only 8% of patients with streptococcal infections. Some patients with clinically evident infection but negative cultures had been treated with antibiotics
before culture. The mean time from clinical onset of infection
to renal disease was 3 weeks (including 4 wk for URT
infection, 3 wk for skin and lung infections, and 2 wk for
endocarditis). In 7 patients (8.1%), comprising 4 with pneumonia, 2 with endocarditis, and 1 with urinary infection, the
onset of GN coincided with the first clinical recognition of
infection. The time from clinically apparent onset of renal
disease to biopsy was 2 months in 62 of 67 patients (92.5%)
with available data.

Clinical Renal Characteristics at Presentation in

70 Patients Without Underlying DGS
Twenty patients (28.6%) had new-onset hypertension,
and 22 additional patients (31.4%) had longstanding
hypertension at the time of biopsy (Table 3). Peripheral
edema was present in approximately half of the patients.
The mean 24 h urine protein was 3.6 g, and 40.7% of
patients had nephrotic range proteinuria. Nephrotic syndrome was present in 29.1% of patients. Hematuria was
present in 89.6% of patients, including macroscopic
hematuria in 23.9%. Red blood cell casts were reported
in only 14.9% of patients. Leukocyturia was present in the
majority of patients. The mean peak serum creatinine was
3.96 mg/dL, while the mean serum creatinine at biopsy was
3.89 mg/dL. Seven patients (10%) had a peak serum
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Medicine  Volume 87, Number 1, January 2008

Acute Postinfectious Glomerulonephritis in Adults

TABLE 1. Demographics and Predisposing Factors For

Infection (86 Patients)
No. of Patients (%)
Male:female
Age, yr (mean SD)
1524
2534
3544
4554
5564
Over 64
Race
White
Hispanic
Black
Asian
Undisclosed
Predisposing factors for infection
Diabetes mellitus
Malignancy
Immunosuppressive therapy
Alcoholism
Cirrhosis
Acquired immunodeficiency
syndrome (AIDS)
Intravenous drug use
Severe malnutrition

57:29 (66.3:33.7)
56 16
3 (3.5)
8 (9.3)
12 (14.0)
16 (18.6)
18 (20.9)
29 (33.7)

Clinical Renal Characteristics at Presentation in

16 Patients With Underlying DGS
Compared to APIGN patients without underlying
DGS, the subgroup of APIGN patients who had underlying
DGS on biopsy exhibited a greater degree of proteinuria
(mean, 4.1 g/24 h), and a higher serum creatinine at baseline
(mean, 2.2 mg/dL) and at the time of renal biopsy (mean,
6.44 mg/dL) (see Table 3). All patients had microhematuria,
while macrohematuria was seen in only 1 patient (6.3%). C3
was depressed in all patients, whereas C4 was low in 53.3%
of patients.

Pathologic Findings

51 (59.3)
13 (15.1)
9 (10.5)
3 (3.5)
10 (11.6)
33 (38.4)
25 (29.1)
4 (4.7)
3 (3.5) (2 had DM,
1 had malignancy)
2 (2.3) (1 had DM)
2 (2.3) (both had DM)
2 (2.3)

The most frequent histologic pattern of glomerular

injury on LM was diffuse endocapillary proliferative and
exudative GN (Figure 1), found in 72.1% of patients, followed by focal endocapillary proliferative and exudative GN
(12.8% of patients), and mesangial proliferative GN (8.1%)
(Table 4). Only 2 patients had an MPGN pattern, including
1 with an infected ventriculoperitoneal shunt and 1 with
staphylococcal skin infection. Diffuse necrotizing and crescentic GN (defined by crescents or necrosis involving
50%
of glomeruli, according to the World Health Organization9)
was seen in 4 patients. Two of these patients had streptococcal endocarditis, of which 1 had C-ANCA seropositivity;
1 had streptococcal URT infection; and 1 had staphylococcal
skin infection.

1 (1.2) (also had DM)

1 (1.2)

LM Findings in 70 Patients Without

Underlying DGS

creatinine in the normal range, 6 of whom had resolving

APIGN on biopsy (3 mesangial proliferative GN and 3
focal endocapillary proliferative GN). More than two-thirds
of patients had serum creatinine >2 mg/dL at biopsy.
Baseline serum creatinine was elevated in only 6 of the 31
patients with available data. Testing for serum complement
(C) was performed in 58 patients, 63.8% of whom had a
depressed C3, 48.3% had a depressed C4, and 67.2% had a
depressed C3 or C4.

The mean glomerular count was 18 (range, 546) and

the mean percentage of sclerotic glomeruli was 9.9%
(Table 5). Glomerular neutrophil infiltration was seen in
90% of cases. Cellular crescents were present in approximately one-third of cases but affected
20% of glomeruli in
only 14.3% of cases. Fibrous crescents, on the other hand,
were less frequent, seen in 12.9% of cases, and affected

20% of glomeruli in only 2 cases. Segmental glomerular
necrosis, characterized by intracapillary fibrin deposition,
rupture of the glomerular basement membrane, and fibrin
extravasation into the Bowman space, was encountered in

TABLE 2. Site of Infection and Infectious Agent (86 Patients)

Site of Infection
Upper respiratory tract
Skin
Pneumonia
Endocarditis
Osteomyelitis
Urinary tract infection
Deep-seated abscess
Ventriculoperitoneal shunt
Phlebitis
No clinical evidence of infection

No. of Patients (%)

20
15
15
10
4
4
2
1
1
14

(23.3)
(17.4)
(17.4)
(11.6)
(4.7)
(4.7)
(2.3)
(1.2)
(1.2)
(16.3)

Infectious Agent

No. of Patients (%)

Streptococcus
Staphylococcus
Pneumococcus
Pseudomonas
Enterococcus
Propionibacterium acnes
Candida
Unknown

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24
21
1
1
1
1
1
36

(27.9)
(24.4)
(1.2)
(1.2)
(1.2)
(1.2)
(1.2)
(41.9)

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TABLE 3. Clinical Characteristics at Presentation (86 Patients)

APIGN Patients Without DGS
No. (%) (n = 70)

APIGN Patients With DGS

No. (%) (n = 16)

New-onset hypertension
Long-standing hypertension
Peripheral edema
Mean 24 h urine protein, g
Proteinuria <1 g/24 h
Proteinuria 13 g/24 h
Proteinuria > 3 g/24 h
Full nephrotic syndrome
Hematuria (microscopic or macroscopic)
Macroscopic hematuria
RBC casts
Leukocyturia
Mean baseline serum creatinine, mg/dL (range)
Mean serum creatinine at biopsy, mg/dL
Creatinine 1.2 mg/dL
Creatinine 1.22 mg/dL
Creatinine > 2 mg/dL
Low C3
Low C4
Low C3 or C4

20/70 (28.6)
22/70 (31.4)
37/70 (52.9)
3.6
13/59 (22.0)
22/59 (37.1)
24/59 (40.7)
16/55 (29.1)
60/67 (89.6)
16/67 (23.9)
10/67 (14.9)
37/67 (55.2)

2/16 (12.5)
8/16 (50.0)
9/15 (60.0)
4.1
4/13 (30.8)
4/13 (30.8)
5/13 (38.5)
3/13 (23.1)
15/15 (100)
1/16 (6.3)
3/14 (21.4)
10/14 (71.4)
2.2 (0.94.4)
6.44
0/16
0/16
16/16 (100)
15/15 (100)
8/15 (53.3)
15/15 (100)

21.4% of cases. Interstitial inflammation with a mixed

infiltrate of lymphocytes, monocytes, plasma cells, and rare
neutrophils was present in 64 cases (91.4%) and was typically
focal. In 3 cases (4.3%) the interstitial neutrophils were numerous, and 5 cases (7.1%) had neutrophil casts. Secondary acute tubular injury with luminal ectasia, epithelial
simplification, loss of brush border, and nuclear enlargement
was a common feature, identified in 60% of cases. The degree
of tubular atrophy and interstitial fibrosis ranged from absent
to mild in the majority of cases. Focal septic vasculitis was
present in 2 cases (2.9%). Arteriosclerosis ranged from absent
(24.2% of cases) to mild (40% of cases) to moderate (32.9%
of cases) to severe (2.9% of cases).

and ranged from mild (1 case) to moderate (11 cases) to

severe (4 cases).

3.89
7/70 (10.0)
15/70 (21.4)
48/70 (68.6)
37/58 (63.8)
28/58 (48.3)
39/58 (67.2)

IF Findings
Standard IF on frozen tissue was performed in 83
biopsies with available glomeruli (Table 7). In 1 of the 3

LM Findings in 16 Patients With

Underlying DGS
Sampling for LM included a mean of 18 glomeruli
(range, 381 glomeruli), and a mean of 21.8% of glomeruli
were globally sclerotic (Table 6). Glomerular neutrophil
infiltration was present in all cases and was typically diffuse.
Cellular crescents and necrosis were seen in one-quarter of
cases, whereas fibrous crescents were not identified. All
cases showed mesangial sclerosis and thickening of glomerular and tubular basement membranes, typical of DGS. The
mesangial sclerosis was nodular in 12 cases (75%) and
diffuse in 4 cases (25%) (Figure 2). The degree of tubular
atrophy and interstitial fibrosis ranged from mild (37.5% of
cases) to moderate (43.8%) to severe (18.8%). Arteriosclerosis and arteriolar hyalinosis were present in all cases

24

FIGURE 1. The most common histologic pattern of adult

APIGN is a diffuse and global endocapillary proliferative glomerulonephritis. The glomerular capillaries are globally occluded
by numerous infiltrating neutrophils, as well as proliferation of
glomerular endothelial and mesangial cells (H & E,  400).
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Medicine  Volume 87, Number 1, January 2008

Acute Postinfectious Glomerulonephritis in Adults

TABLE 4. Histologic Pattern on LM (86 Patients)

No. of Patients (%)
Mesangial proliferative GN
Focal proliferative GN
Diffuse proliferative GN
MPGN
Crescentic and necrotizing GN*

7
11
62
2
4

(8.1)
(12.8)
(72.1)
(2.3)
(4.6)

*Defined by the presence of crescents and/or necrosis affecting
50% of

glomeruli.

remaining biopsies lacking glomeruli on frozen tissue, IF

was performed on pronase-digested paraffin-embedded
tissue, a less sensitive technique for detecting C3 tissue deposition31. The most common staining pattern on IF, seen
in 82% of cases, was granular mesangial and glomerular
capillary wall, resembling the starry sky pattern described
by Sorger et al51 (Figure 3). In 7 cases (8.4%), the staining
was predominantly glomerular capillary wall garland
pattern. In the remaining 8 cases (9.6%), only mesangial
positivity was detected, mesangial pattern. Of the 8 cases
with mesangial pattern, 3 had features of resolving APIGN
on LM (2 mesangial proliferative GN and 1 focal
proliferative GN), 1 showed necrotizing and crescentic GN,
and 4 showed diffuse proliferative GN including 3 with
underlying DGS. C3 was positive in all 84 cases (100%) and
was the dominant or codominant immune reactant detected
in glomeruli in all 83 cases in which IF was performed on
frozen tissue, with a mean staining intensity of 2.4+. The
most common immunoglobulin deposited in glomeruli was
IgG (mean intensity when positive, 1.3+) present in 65.5% of
cases. IgM staining was less frequent (44% of cases) and less
intense (mean intensity when positive, 1.0+). In 8 cases
(9.6%), IgM staining was stronger than IgG and IgA, 3 of
which were associated with URT infection, 3 with endocarditis, and 2 with unknown infection sites. Glomerular IgA

staining was detected in 44% of cases with a mean intensity

when positive of 1.3+. In 8 cases (9.6%), IgA was the
dominant immunoglobulin deposited in glomeruli (intensity

1+), 7 of which were from patients with staphylococcal
infection and underlying DGS. The remaining case was from
a nondiabetic subject with an undetermined pathogen. C1q
deposition was detected in approximately one-third of cases
but was of low intensity (mean, 0.8+). Staining for kappa and
lambda was similar with regard to frequency and intensity.
Diabetic patients with or without nephropathy commonly
showed weak linear staining of glomerular and tubular
basement membranes for IgG and albumin.

EM Findings
EM was performed on all 83 biopsies with available
glomeruli (Table 8). Subepithelial electron dense deposits
were present in 94% of cases, and typically exhibited a
hump-shaped appearance (Figure 4). Subepithelial humps
were also seen with the trichrome-stained LM sections in 2
of the 3 biopsies lacking glomeruli for EM. In patients with
underlying DGS, the subepithelial deposits were small and
sparse. In cases of resolving APIGN, the subepithelial
deposits were preferentially located at the glomerular basement membrane reflection over the mesangium (that is, the
mesangial waist). Subendothelial deposits were typically
small and infrequent, but were nonetheless detectable in
three-quarters of cases. Mesangial deposits were found in
90.4% of cases and were abundant in 55.4% of cases. By
definition, patients with underlying DGS displayed mesangial sclerosis and thickening of the glomerular and tubular
basement membranes. The mean degree of foot process
effacement was 60% (range, 15%100%).

Outcome
Clinical follow-up was available in 66 patients (76.7%)
(Table 9). The duration of follow-up was <1 month in
8 patients (12.1%), 1 to <3 months in 10 patients (15.1%),
and
3 months in 48 patients (72.7%). The mean duration of

TABLE 5. LM Findings of 70 APIGN Patients Without Underlying DGS

Pathologic Findings

No. of Cases

No. of glomeruli, mean (SE)

No. of sclerotic glomeruli, mean (SE)
Sclerotic glomeruli, % (SE)
No. of cases with glomerular neutrophil infiltration (focal/diffuse)
No. of cases with cellular crescents (<20% of glomeruli,
20% of glomeruli)
No. of cases with fibrous crescents (<20% of glomeruli,
20% of glomeruli)
No. of cases with necrosis (<20% of glomeruli,
20% of glomeruli)
Interstitial inflammation: none/focal/diffuse*
Acute tubular injury: none/focal/diffuse*
Tubular atrophy and interstitial fibrosis: none/mild/moderate/severey
Arteriosclerosis and arteriolar hyalinosis: none/mild/moderate/severe

18 (1.3)
2 (0.5)
9.9 (1.6)
63 (21/42)
26 (16, 10)
9 (7, 2)
15 (8, 7)
6/58/6
28/27/15
30/33/5/2
17/28/23/2

90.0 (33.3/66.7)
37.1 (61.5, 38.5)
12.9 (77.8, 22.2)
21.4 (53.3, 46.7)
8.6/82.9/8.6
40.0/38.6/21.4
42.9/47.1/7.1/2.9
24.2/40.0/32.9/2.9

Abbreviation: SE = standard error.

*Definitions: focal, 50% of cortical surface area; diffuse, >50%.
y
Definitions: mild, 0%25% of cortical surface area; moderate, 26%50%; severe, >50%.

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Medicine  Volume 87, Number 1, January 2008

Nasr et al

TABLE 6. LM Findings of 16 APIGN Patients With Underlying DGS

Pathologic Finding

No. of Cases

No. of glomeruli, mean (SE)

No. of sclerotic glomeruli, mean (SE)
Sclerotic glomeruli, % (SE)
Pattern of DGS: nodular/diffuse
No. of cases with glomerular neutrophil infiltration (focal/diffuse)
No. of cases with cellular crescents (<20% of glomeruli,
20% of glomeruli)
No. of cases with necrosis (<20% of glomeruli,
20% of glomeruli)
Interstitial inflammation: none/focal/diffuse
Acute tubular injury: none/focal/diffuse
Tubular atrophy and interstitial fibrosis: mild/moderate/severe
Arteriosclerosis and arteriolar hyalinosis: mild/moderate/severe

18 (4.5)
6 (3)
21.8 (4)
12/4
16 (3/13)
4 (3, 1)
4 (4, 0)
1/13/2
5/7/4
6/7/3
1/11/4

75/25
100 (18.8/81.2)
25.0 (75.0, 25.0)
25.0 (100, 0)
6.3/81.3/12.5
31.2/43.8/25.0
37.5/43.8/18.8
6.3/68.8/25.0

Abbreviations and definitions: See Table 5.

follow-up for all 66 patients was 19 months. Of the 18

patients with <3 months of follow-up, 4 achieved complete
remission, 8 had persistent renal dysfunction (1 of whom
died of septicemia), and 6 remained dialysis dependent,
including 5 patients who died (3 due to septicemia and
multiorgan failure and 2 of undetermined causes).
For the purpose of outcome analysis, only patients with
a follow-up of
3 months (48 patients) and patients with <3
months of follow-up and complete remission (4 patients)
were included. Eleven of the 52 patients had underlying
DGS. The mean duration of follow-up for the 48 patients
with
3 months of follow-up was 25 months (range, 3120
mo). Of the 41 APIGN patients without underlying DGS,
23 (56.1%) achieved complete remission, 11 (26.8%) had
persistent renal dysfunction, and 7 (17.1%) progressed to
ESRD including 2 patients who died, 1 of septicemia and 1
of multiple myeloma. In this group without underlying DGS,
on univariate analysis of 3-way outcome (complete remission vs. persistent renal dysfunction vs. ESRD), correlates of
complete remission were younger age, female sex, lower
serum creatinine at time of biopsy, and the absence of
immunocompromised state. There were no significant
correlates between renal outcome and site of infection (p =
0.07) or infectious organism (p = 0.31) or any other
demographic, clinical, or serologic factor. Similarly, there
were no significant pathologic correlates of renal outcome,
although patients with complete remission showed less
interstitial inflammation and less acute tubular injury than
the other 2 groups (both p = 0.051).
Correlates of serum creatinine >2 mg/dL at biopsy on
univariate analysis included older age, male sex, history of
pre-existing hypertension, lower serum albumin, a low C4,
and greater endocapillary proliferation, interstitial inflammation, acute tubular injury, and more cellular crescents. On
multivariate analysis, only a lower serum albumin (p =
0.015), low C4 (p = 0.002), interstitial inflammation (p =
0.012), endocapillary proliferation (p = 0.039) and acute
tubular injury (p = 0.015) remained significant. The presence
of cellular crescents on biopsy did not correlate with risk of

26

ESRD (p = 0.071). A diffuse endocapillary proliferative

pattern correlated with presence of nephrotic syndrome (p =
0.021).
By multivariate analysis (binary logistic regression
analysis), age (hazard ratio [HR], 0.938; 95% confidence
interval [CI], 0.8890.989; p = 0.017) and serum creatinine
at biopsy (HR, 0.746; 95% CI, 0.5570.999; p = 0.049) were
significant and independent inverse correlates of complete
remission, and higher serum creatinine at biopsy (HR, 1.486;
95% CI, 1.0332.137; p = 0.033) correlated with ESRD. By
multinomial logistic regression analysis, age was the only
clinical characteristic that distinguished complete remission
from persistent renal dysfunction (HR, 1.068; 95% CI,
1.0061.132; p = 0.030) and ESRD (HR, 1.087; 95% CI,
1.0021.180; p = 0.046). Serum creatinine at biopsy was
lower in patients with complete remission versus ESRD (HR,
1.659; 95% CI, 1.0462.629; p = 0.03), as was percentage

FIGURE 2. An example of APIGN superimposed on diabetic

glomerulosclerosis illustrates the combination of severe glomerular neutrophil infiltration and distinct mesangial nodules
of sclerosis (H & E,  400).
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Medicine  Volume 87, Number 1, January 2008

Acute Postinfectious Glomerulonephritis in Adults

TABLE 7. Glomerular Findings on IF (84 Cases)

No. of Positive Cases
(%)
IgG
IgM
IgA
C3
C1
Kappa
Lambda

55
37
37
84
30
57
59

(65.5)
(44.0)
(44.0)
(100)
(35.7)
(67.9)
(70.2)

TABLE 8. EM Findings (83 Cases)

Mean Intensity
When Positive*
1.3+
1.0+
1.3+
2.4+
0.8+
1.3+
1.3+

*Scale: trace (0.5%), 13+.

of global sclerosis (HR, 1.072; 95% CI, 1.0011.148; p =

0.048).
Thirty-three percent of the 52 patients with outcome
data were treated with steroids. The indication for steroid
therapy was renal insufficiency with or without crescents. Of
this group, 70% had complete remission, 18% had persistent
renal dysfunction, and 12% progressed to ESRD. No
correlation was found between steroid therapy and renal
outcome: the 17 steroid-treated patients included 16 of 35
nondiabetics and 1 of 16 diabetics (p = 0.009). When patients
with underlying DGS were excluded from the analysis,
complete remission occurred in 12 of 17 patients treated with
steroids versus 10 of 23 non-steroid-treated patients (p =
0.116). Thirty-five patients were known to have been treated
with antibiotics. There was not sufficient information about
the adequacy of antibiotic therapy to draw conclusions
about outcome.
Of the 11 patients with underlying DGS, 2 (18.2%) had
persistent renal dysfunction and the remaining 9 (81.8%)
progressed to ESRD, including 2 patients who died due to
septicemia. This was a much poorer renal outcome than

FIGURE 3. A representative immunofluorescence image

shows coarsely granular positivity (starry sky pattern) in a
global glomerular capillary wall and mesangial distribution.
(Anti-IgG,  400).

No. of Cases

75 (29/46)
62 (41/21)
78 (45/33)
75

90.4
74.7
94
90.4

Mesangial deposits (segmental/global)

Subendothelial deposits (segmental/global)
Subepithelial deposits (segmental/global)
Subepithelial humps

that of patients without underlying DGS (p < 0.001). None

of these patients was treated with steroids.

DISCUSSION
In the current study we analyze the clinical, pathologic,
and outcome data in a series of 86 adults with nonepidemic
APIGN. To our knowledge, this is the largest biopsy-based
series and the only North American series in the modern era.
Previous studies have suggested that the incidence of APIGN
in Western Europe is declining, likely due to an improved
standard of living and earlier treatment of pharyngeal
infections49. The biopsy incidence of adult APIGN in the
current study was lower than that reported in 3 relatively
recent European studies (0.6% vs. 1.7%4.6%)21,28,29

FIGURE 4. The most characteristic ultrastructural finding is

hump-shaped subepithelial deposits involving the peripheral
glomerular capillary walls and mesangial waist. The deposits are
large, without intervening spikes. There is localized effacement
of foot processes overlying the humps. (Electron micrograph,
 2000).

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27

Medicine  Volume 87, Number 1, January 2008

Nasr et al

TABLE 9. Outcome and Prognostic Indicators* in 41 Patients

Without Underlying DGS
CR
No. of patients
Percentage of patients
Age (yr)
Male:Female
Immunocompromised state, %
Serum creatinine, mg/dL
Baseline
At biopsy
Follow-up
UVp, g/24 h
At biopsy
Follow-up
Glomerulosclerosis, %
Interstitial inflammation
Acute tubular injury score (02+)
TA-IF average score (03+)

PRD ESRDy p Value

23
11
7
56.1% 26.8% 17.1%
46.5 62.9 63.6
11:12 8:3
7:0
9
55 29

0.005
0.029
0.011

1.1
3.0
1.1

0.9
4.8
2.0

1.4
6.6
10.0

0.076
0.006
<0.001

4.25
0.64
9.7
1.1
0.7
0.6

2.77
1.02
10.5
1.6
1.2
0.7

4.43
5.13
22.4
1.9
0.9
1.3

NS
NS
NS
0.051
0.051
0.106

Abbreviations: CR = complete renal recovery, PRD = persistent renal

dysfunction (renal insufficiency), ESRD = end-stage renal disease, UVp =
urinary protein excretion, NS = not significant, TA-IF = tubular atrophy and
interstitial fibrosis.
*On univariate analysis. Patients had a follow-up of
3 months or <3
months with CR.
y
Two patients with ESRD died.

(Table 10). In our patient population, there was a male

predominance (2:1), similar to other studies12,21,28,29,40. The
percentage of adult patients older than 64 years in the current
study was 33.7%, compared with 5.6% in the classic 1974
study by Baldwin et al4 from New York City, 3.8% in the
1979 report by Lien et al23 from South Australia, and 0% in
the 1942 study by Ellis14 and the 1936 study by Richter40.
A longer life expectancy coupled with an increasing
prevalence of comorbid conditions such as diabetes likely
accounts for the predominance of elderly patients in the
current cohort.
Most cases of APIGN reported in the literature from
1960 to 1980 occurred in patients without significant past
medical history4,23,26. In the 1980s, an important association
between intravenous drug use (IVDU) and endocarditis was
appreciated in the United States34. Other factors predisposing
to infection have been documented in a substantial fraction
of patients described in more recent studies. In Western
Europe, alcoholism has become the most important risk
factor for APIGN, found in 12%57% of patients21,28,29 (see
Table 10). In the current study, over one-third of patients had
1 or 2 predisposing factors for infection; diabetes was by far
the most frequent factor, found in 29.1% of patients. Only
2 patients were alcoholics (2.3%), 1 of whom was also
diabetic. Only 1 patient had a history of IVDU, and this
patient was also diabetic.
Classically, APIGN occurs after streptococcal pharyngitis or skin infection4,26. More recently, other sites of

28

infection and more diverse organisms have been linked to

adult APIGN. Considering all 242 patients compiled from
the current study and the 3 modern European studies, the
sites of infection included URT in 59 patients (24%), skin in
39 (16%), lung in 33 (14%), endocarditis in 21 (9%), and
teeth in 17 (7%). The responsible bacterium was streptococcus in 68 patients (28%), staphylococcus in 44 patients
(17%), and Gram-negative bacteria in 25 patients (10%).
Importantly, 7%16% of patients had no clinical evidence of
infection preceding the renal disease, and in 24%59% of
patients the offending microorganism was not identified (see
Table 10). These latter data indicate that APIGN should be
included in the clinical differential diagnosis of nephritic
syndrome in adults, especially in patients with diabetes or
alcoholism, even in the absence of a history of infection. The
latent period between the streptococcal infection and the
onset of renal disease was reported to be shorter after URT
infection (13 wk) than after skin infection (36 wk)11,30,35.
In contrast, in our cohort the mean latent period after URT
infection was 4 weeks compared with 3 weeks after skin and
lung infections and 2 weeks after endocarditis. We note that
in many cases infection was only discovered at the time
APIGN was diagnosed, indicating that the infection may go
unrecognized for some time. In 20% of patients with
endocarditis and 27% of patients with pneumonia in the
current study and in 19% of patients with endocarditis
reported by Majumdar et al24, the renal disease was diagnosed at the same time as the infection. Srivastava et al53
reported 11 children in whom pneumonia and APIGN
occurred within 72 hours of each other.
The classic glomerular pattern of injury associated
with infection, particularly after transient acute streptococcal
pharyngitis or pyoderma, is diffuse endocapillary proliferative and exudative GN. This pattern was present in
approximately three-quarters of patients in the current study.
Focal endocapillary and exudative GN and mesangioproliferative GN were less common, seen in 12.8% and 8.1% of
patients, respectively. The latter 2 patterns likely represent
the resolving phases of the disease11,42, although some cases
with these milder degrees of injury never develop more
severe lesions11. Cellular crescents were present in about
one-third of cases but affected >25% of glomeruli in only 9%
of cases. In contrast, one-third of cases reported by Montseny
et al28 showed crescents in >25% of glomeruli.
By IF, the glomerular deposits stained dominantly for
C3 (mean intensity, 2.4+) with weaker and more focal
staining for IgG (mean intensity, 1.3+). These findings are
similar to those reported by others11. An explanation of this
staining pattern is that the presumed nephritogenic antigen of
APIGN, the streptococcal pyogenic exotoxin B (SPE B), is a
cationic cysteine proteinase that can bind directly to the
glomerular basement membrane through charge interactions
without formation of immune complexes5. The nephritogenic
antigen or antigens appear to activate complement by the
alternative or lectin pathways rather than through classical
pathway activation on IgG41.
Crescentic and necrotizing GN was seen in 4 patients
(4.6%), 2 of whom had endocarditis, including 1 with C-ANCA
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Medicine  Volume 87, Number 1, January 2008

Acute Postinfectious Glomerulonephritis in Adults

TABLE 10. Current Spectrum of Nonepidemic APIGN in Adults, Present and Recent Reports
First Author (ref )
Keller (21)
Period of study
Country
No. of patients
Biopsy incidence, %
Median age (yr)
M:F
Patients with alcoholism, %
Patients with diabetes, %
Most common site of
infection (%)
Most common bacteria (%)

Patients with no clinical

evidence of infection, %
Patients with no identifiable
offending microorganism, %
Follow-up, mo (mean)
CR, %
PRD, %
ESRD, %
Death, %
Correlates of renal outcome
CR

PRD

19841993
Germany
30
4.5
49
3:1
57
NA
Teeth (23) Skin (13)

Montseny (28)

Moroni (29)

19761993
France

19791999
Italy

76
4.6
NA
2.4:1
30
8
URT (28) Skin (25)
Lung (18)
Teeth (13)
Endocarditis (13)
Streptococcus* (40)
Staphylococcus (17)
Staphylococcus (13)
Gram-negative
bacteria (14)
Streptococcus* (14)
10
7

50
1.7
54
1.5:1
12
10
URT (44) Lung (16)
Urinary tract (12)
Streptococcus* (47)
Gram-negative
bacteria (22)
Staphylococcus (12)
12

Nasr (Present Report)

19952005
United States
86
0.6
58
2:1
2
29
URT (23) Skin (17.5)
Lung (17.5)
Endocarditis (12)
Streptococcus* (28)
Staphylococcus (24)
16

43

59

24

42

176 (12.5)
64
28
4
4

1108
28
53
8
11

20138 (90)
43
47
10
10

3120 (25)y
56
27
17
5

Alcoholismx,
crescentic
glomerulonephritisx

ESRD

Absence of underlying
Age <40 yr, URT
Younger agez, female
diseasez, absence of
infection, endocapillary
sex, absence of
hypercellularity,
immunocompromised
interstitial inflammationz,
Starry sky pattern
state, lower serum
absence of crescents,
creatinine at biopsyz,
absence of subendothelial
deposits
absence of interstitial
inflammation
Nephrotic syndrome,
crescentic
glomerulonephritis,
interstitial fibrosis
Higher serum
creatinine
at biopsyz,
underlying DGS

Abbreviations: See previous tables. NA = not available.

*Determined by elevated ASLO titers and/or culture.
y
Only the 41 patients without underlying DGS who had a follow-up
3 mo (37 patients) or <3 mo with CR (4 patients) were included for outcome analysis.
z
By multivariate analysis.
x
Chronic renal dysfunction was more common in patients with alcoholism and those with crescentic glomerulonephritis, although statistical analysis was
not performed.

seropositivity. These 2 cases showed extracapillary proliferation (without significant endocapillary hypercellularity)
and prominent tuft necrosis on LM, glomerular deposition
of C3 with or without IgG on IF, and exclusively mesangial
deposits on EM. The remaining 8 patients with endocarditis
(80%) had diffuse endocapillary proliferative and exudative

GN. In a 2000 study from the United Kingdom, Majumdar

et al24 analyzed the renal pathologic findings in 62 patients
with infectious endocarditis. Sixteen patients had GN,
diagnosed on biopsy in 9 and on autopsy on 7. In contrast
to our findings, pauci-immune crescentic and necrotizing
vasculitic GN was the most frequent pattern, present in

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29

Medicine  Volume 87, Number 1, January 2008

Nasr et al

11 patients (69%). Of the remaining 5 patients, 3 (19%) had

diffuse endocapillary proliferative GN and 2 (12%) had
MPGN24. In the older literature, focal GN was the most
common pattern associated with endocarditis, although
diffuse proliferative GN was not infrequent3,6,34. Only
2.3% of patients in the current study and 8% of patients
reported by Montseny et al28 showed MPGN, attesting to the
rarity of this morphologic pattern in patients with infection.
MPGN is encountered in the majority of patients with shunt
nephritis and rarely in association with pneumonia, deepseated infections, and osteomyelitis11,17,28,55.
Multiple studies with long follow-up have shown that
the majority of children and patients with the epidemic form
of APIGN have an excellent prognosis13,19,38,45. In a 2001
Japanese study, Kasahara et al19 followed 138 children with
nonepidemic APIGN diagnosed based on the presence of
hematuria, transient hypocomplementemia, and evidence of
group A beta-hemolytic streptococcal infection. None of the
patients had renal insufficiency. All patients had normalization of serum complement within 12 weeks, disappearance of
hematuria within 4 years, and disappearance of proteinuria
within 3 years19. In a study of 534 children and adults with
APIGN in Trinidad (361 epidemic and 173 sporadic), 96.5%
had complete recovery after 1217 years of follow-up38. Not
all APIGN epidemics are associated with good outcome. A
2005 prospective study from Brazil of 56 patients, mostly
adults, who had acute GN following an outbreak of group C
Streptococcus zooepidemicus found a less favorable longterm outcome47. After a mean follow-up of 5.4 years, 30% of
patients were hypertensive, 49% had reduced creatinine
clearance, and 22% had microalbuminuria47. Poor outcomes
also have been reported in adults with nonepidemic APIGN.
According to the older literature, the rate of complete
remission ranges from 53% to 76%22,30,40. Considering the 3
recently reported studies from Europe and the current study,
28%64% of patients recovered completely, 27%53% had
persistent renal dysfunction, 4%17% progressed to ESRD,
and 4%11% died21,28,29 (see Table 10). The poor outcomes
in the modern era likely relate to older patient age and more
frequent comorbidities. The statistically significant histologic and clinical predictors of renal outcome are listed in
Table 10. On multivariate analysis, performed only in the
current study and the study by Moroni et al29, correlates of
complete remission were younger age, lower serum creatinine at biopsy, absence of underlying disease (specifically
DGS in our study), and the absence of interstitial inflammation (which was of borderline statistical significance
in our univariate analysis but did not hold up in a multivariate analysis that incorporated age and serum creatinine
into the model). The only significant predictor on multivariate modeling of ESRD in our study was a higher serum
creatinine at biopsy.
Previous studies in which statistical analysis was not
performed reported that the presence of abundant crescents
was associated with poor outcome10,52,57, whereas in the
current study crescents did not correlate with outcome. The
lack of detectable impact of crescents on clinical outcome
may have been the result of the small percentage of

30

glomeruli with crescents (only 9% of cases showed crescents

affecting >25% of glomeruli, and 4.6% of cases showed
crescents affecting >50% of glomeruli).
The efficacy of immunosuppressive therapy for
APIGN is controversial. Roy et al43 compared the outcome
in 5 children with crescentic poststreptococcal GN who were
treated with prednisone, azathioprine, cyclophosphamide,
dipyridamole, and heparin followed by warfarin to that in 5
children who were managed with supportive care only. They
found that quintuple therapy offered no advantage over
supportive care43. Evidence supporting the use of steroid
therapy for crescentic APIGN is largely anecdotal39,54,57.
Although a significant subgroup (33% of patients) in the
current study received steroid therapy for variable periods of
time, no correlation could be found between this form of
therapy and outcome.
APIGN is one of the most common diseases to occur
superimposed on DGS, although only limited data are available
concerning the clinical and pathologic features and outcome of
this dual glomerulopathy25. Thirty cases have been reported
that we know of; most include only 13 patients, and all but 146
were reported before 19901,2,7,8,15,20,27,36,37,44,46,48,56. Of the 21
patients with available data, 15 had preceding streptococcal
infection and 6 had staphylococcal infection. In contrast,
among the 16 adults with APIGN and DGS in the current study
(which, to our knowledge, represents the largest reported
cohort to date), 10 were secondary to staphylococcus and only
3 were due to streptococcus. Patients with diabetes have a high
incidence of staphylococcal infection, especially of lower
extremity skin and bone, due to higher colonization and more
frequent skin ulcerations. As we previously reported32,33 and
re-encountered in this study, the pathologic findings of
APIGN in patients with underlying DGS differ from those
in patients with pure APIGN in the predominance of
mesangial and subendothelial deposits with few small
subepithelial deposits. Moreover, IgA is the dominant
immunoglobulin detected in glomeruli in the majority of
cases, especially those with staphylococcal infection. We
hypothesize that the formation of large, hump-shaped,
subepithelial deposits is hindered by the thickened glomerular
basement membranes of underlying DGS. IgA dominance can
make it difficult to distinguish this histologic variant of
APIGN from IgA nephropathy. Features that favor IgAdominant APIGN over IgA nephropathy include depressed
serum complement levels, diffuse endocapillary proliferative
and exudative GN on LM, and subepithelial hump-shaped
deposits on EM32,33,46. The outcome of APIGN in patients
with underlying DGS is dismal, with 9 of 11 patients in the
current study progressing to ESRD. Similar poor outcomes
have been reported by others7,27,46. Follow-up was available
in 15 of the 30 cases reported by other investigators2,7,27,36,46,56.
Of these, 8 patients became dialysis dependent, 3 had persistent renal dysfunction, 3 had complete remission, and 1 died
shortly after diagnosis.
In conclusion, the epidemiology of adult APIGN is
shifting. Diabetes and aging have emerged as major risk
factors. Among infectious agents, staphylococcus has become
nearly as common as streptococcus, and is the most frequent
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Medicine  Volume 87, Number 1, January 2008

agent in diabetics. Our data indicate that the overall prognosis

of adult APIGN is guarded. Over a fourth of patients will have
persistent renal dysfunction and close to a fifth will progress
to ESRD. Outcome is particularly poor in patients with
underlying DSG, of whom >80% can be expected to develop
ESRD. As the population ages and diabetes becomes epidemic
throughout the industrialized world, the incidence of adult
APIGN is likely to increase.
ACKNOWLEDGMENT
We thank our many clinical colleagues who kindly
provided follow-up data on their patients.
REFERENCES
1. Amoah E, Glickman JL, Malchoff CD, Sturgill BC, Kaiser DL, Bolton
WK. Clinical identification of nondiabetic renal disease in diabetic
patients with type I and type II disease presenting with renal dysfunction. Am J Nephrol. 1988;8:204211.
2. Aziz S, Cohen AH, Winer RL, Llach F, Massry SG. Diabetes mellitus
with immune complex glomerulonephritis. Nephron. 1979;23:3237.
3. Baehr G. Glomerular lesions of subacute bacterial endocarditis. J Exp
Med. 1912;15:330347.
4. Baldwin DS, Gluck MC, Schacht RG, Gallo G. The long-term course of
poststreptococcal glomerulonephritis. Ann Int Med. 1974;80:342358.
5. Batsford SR, Mezzano S, Mihatsch M, Schiltz E, Rodriguez-Iturbe
B. Is the nephritogenic antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH? Kidney Int. 2005;
68:11201129.
6. Bell ET. Glomerular lesions associated with endocarditis. Am J Pathol.
1932;8:639663.
7. Bertani T, Mecca G, Sacchi G, Remuzzi G. Superimposed nephritis: a
separate entity among glomerular diseases? Am J Kidney Dis. 1986;7:
205212.
8. Cavallo T, Pinto JA, Rajaraman S. Immune complex disease complicating diabetic glomerulosclerosis. Am J Nephrol. 1984;4:347354.
9. Churg J, Bernstein J, Glassock RJ. Renal Disease: Classification and
Atlas of Glomerular Diseases. New York:Igaku-Shoin; 1995
10. Cunningham RJ III, Gilfoil M, Cavallo T, Brouhard BH, Travis LB,
Berger M, Petrusick T. Rapidly progressive glomerulonephritis in
children: a report of thirteen cases and a review of the literature. Pediatr
Res. 1980;14:128132.
11. DAgati VD, Jennette JC, Silva FG. Atlas of Nontumor Pathology: NonNeoplastic Kidney Diseases. Washington, DC: American Registry of
Pathology-Armed Forces Institute of Pathology; 2005:269296.
12. Dodge WF, Spargo BH, Bass JA, Travis LB. The relationship between
the clinical and pathologic features of poststreptococcal glomerulonephritis. A study of the early natural history. Medicine (Baltimore). 1968;
47:227267.
13. Drachman R, Aladjem M, Vardy PA. Natural history of an acute
glomerulonephritis epidemic in children. An 11- to 12-year follow-up.
Isr J Med Sci. 1982;18:603607.
14. Ellis A. Natural history of Brights disease. Lancet. 1942;1:17.
15. Epstein SE, Becker EL. Acute glomerulonephritis in an adult with
longstanding diabetes mellitus. Ann Intern Med. 1961;54:97103.
16. Haas M. Postinfectious glomerulonephritis complicating diabetic nephropathy: a frequent association, but how clinically important? Hum
Pathol. 2003;34:12251227.
17. Haffner D, Schindera F, Aschoff A, Matthias S, Waldherr R, Scharer K.
The clinical spectrum of shunt nephritis. Nephrol Dial Transplant.
1997;12:11431148.
18. Jennings RB, Earle DP. Post-streptococcal glomerulo-nephritis: histopathologic and clinical studies of the acute, subsiding acute and early
chronic latent phases. J Clin Invest. 1961;40:15251595.
19. Kasahara T, Hayakawa H, Okubo S, Okugawa T, Kabuki N, Tomizawa
S, Uchiyama M. Prognosis of acute poststreptococcal glomerulonephritis (APSGN) is excellent in children, when adequately diagnosed.
Pediatr Int. 2001;43:364367.

Acute Postinfectious Glomerulonephritis in Adults

20. Kasinath BS, Mujais SK, Spargo BH, Katz AI. Nondiabetic renal disease in patients with diabetes mellitus. Am J Med. 1983;75:
613617.
21. Keller CK, Andrassy K, Waldherr R, Ritz E. Postinfectious glomerulonephritisis there a link to alcoholism? Q J Med. 1994;87:97102.
22. Kushner DS, Armstrong SH, Dubin A, Szanto PB, Markowitz A,
Maduros BP, Levine JM, River GL, Gynn TN, Pendras JP. Acute
glomerulonephritis in the adult. Longitudinal, clinical, functional and
morphologic studies of rates of healing and progression to chronicity.
Medicine (Baltimore). 1961;40:203240.
23. Lien JWK, Mathew TH, Meadows R. Acute poststreptococcal glomerulonephritis in adults: a long-term study. Q J Med. 1979;48:99111.
24. Majumdar A, Chowdhary S, Ferreira MA, Hammond LA, Howie AJ,
Lipkin GW, Littler WA. Renal pathological findings in infective
endocarditis. Nephrol Dial Transplant. 2000;15:17821787.
25. Mazzucco G, Bertani T, Fortunato M, Bernardi M, Leutner M, Boldorini
R, Monga G. Different patterns of renal damage in type 2 diabetes
mellitus: a multicentric study on 393 biopsies. Am J Kidney Dis. 2002;
39:713720.
26. McCluskey RT, Baldwin DS. Natural history of acute glomerulonephritis. Am J Med. 1963;35:213230.
27. Monga G, Mazzucco G, di Belgiojoso GB, Confalonieri R, Sacchi G,
Bertani T. Pattern of double glomerulopathies: a clinicopathologic study
of superimposed glomerulonephritis on diabetic glomerulosclerosis.
Mod Pathol. 1989;2:407414.
28. Montseny JJ, Meyrier A, Kleinknecht D, Callard P. The current
spectrum of infectious glomerulonephritis. Experience with 76 patients
and review of the literature. Medicine (Baltimore). 1995;74:6373.
29. Moroni G, Pozzi C, Quaglini S, Segagni S, Banfi G, Baroli A, Picardi L,
Colzani S, Simonini P, Mihatsch MJ, Ponticelli C. Long-term prognosis
of diffuse proliferative glomerulonephritis associated with infection in
adults. Nephrol Dial Transplant. 2002;17:12041211.
30. Nadasdy T, Silva FG. Acute postinfectious glomerulonephritis and
glomerulonephritis caused by persistent bacterial infection. In: Jennette
JC, Olson JL, Schwartz MM, Silva FG, eds. Heptinstalls Pathology of the
Kidney. 6th ed. Philadelphia:Lippincott Williams & Wilkins; 2007:321396.
31. Nasr SH, Galgano SJ, Markowitz GS, Stokes MB, DAgati VD.
Immunofluorescence on pronase-digested paraffin sections: a valuable
salvage technique for renal biopsies. Kidney Int. 2006;70:21482151.
32. Nasr SH, Markowitz GS, Whelan JD, Albanese JJ, Rosen RM, Fein DA,
Kim SS, DAgati VD. IgA-dominant acute poststaphylococcal glomerulonephritis complicating diabetic nephropathy. Hum Pathol. 2003;34:
12351241.
33. Nasr SH, Share DS, Vargas MT, DAgati VD, Markowitz GS. Acute
poststaphylococcal glomerulonephritis superimposed on diabetic glomerulosclerosis. Kidney Int. 2007;71:13171321.
34. Neugarten J, Baldwin DS. Glomerulonephritis in bacterial endocarditis.
Am J Med. 1984;77:297304.
35. Nordstrand A, Norgren M, Holm SE. Pathogenic mechanism of acute
post-streptococcal glomerulonephritis. Scand J Infect Dis. 1999;31:
523537.
36. Olivero J, Suki WN. Acute glomerulonephritis complicating diabetic
nephropathy. Arch Intern Med. 1977;137:732734.
37. ONeill WM, Wallin JD, Walker PD. Hematuria and red cell casts in
typical diabetic nephropathy. Am J Med. 1983;74:389395.
38. Potter EV, Lipschultz SA, Abidh S, Poon-King T, Earle DP. Twelve to
seventeen-year follow-up of patients with poststreptococcal acute
glomerulonephritis in Trinidad. N Engl J Med. 1982;307:725729.
39. Raff A, Hebert T, Pullman J, Coco M. Crescentic post-streptococcal
glomerulonephritis with nephrotic syndrome in the adult: is aggressive
therapy warranted? Clin Nephrol. 2005;63:375380.
40. Richter AB. Prognosis in acute glomerular nephritis. Ann Intern Med.
1936;9:10571069.
41. Rodriguez-Iturbe B, Batsford S. Pathogenesis of poststreptococcal
glomerulonephritis a century after Clemens von Pirquet. Kidney Int.
2007;71:10941104.
42. Rosenberg HG, Vial SU, Pomeroy J, Figueroa S, Donoso PL, Carranza
C. Acute glomerulonephritis in children. An evolutive morphologic and
immunologic study of the glomerular inflammation. Pathol Res Pract.
1985;180:633643.
43. Roy S III, Murphy WM, Arant BS Jr. Poststreptococcal crescenteric

n 2008 Lippincott Williams & Wilkins

Copyright @ Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

31

Medicine  Volume 87, Number 1, January 2008

Nasr et al

44.
45.
46.
47.
48.
49.
50.

32

glomerulonephritis in children: comparison of quintuple therapy versus

supportive care. J Pediatr. 1981;98:403410.
Sabnis SG, Antonovych TT. Diabetic nephropathy with superimposed
immune complex glomerulonephritis. South Med J. 1983;76:456461.
Sanjad S, Tolaymat A, Whitworth J, Levin S. Acute glomerulonephritis
in children: a review of 153 cases. South Med J. 1977;70:12021206.
Satoskar AA, Nadasdy G, Plaza JA, Sedmak D, Shidham G, Hebert L,
Nadasdy T. Staphylococcus infection-associated glomerulonephritis
mimicking IgA nephropathy. Clin. J Am Soc Nephrol. 2006;1:11791186.
Sesso R, Pinto SW. Five-year follow-up of patients with epidemic
glomerulonephritis due to Streptococcus zooepidemicus. Nephrol Dial
Transplant. 2005;20:18081812.
Sharma HM, Yum MN, Kleit S. Acute glomerulonephritis with diabetes
mellitus: report of a case. Arch Pathol. 1974;97:152154.
Simon P, Ramee MP, Autuly V, Laruelle E, Charasse C, Cam G, Ang
KS. Epidemiology of primary glomerular diseases in a French region.
Variations according to period and age. Kidney Int. 1994;46:11921198.
Soni SS, Gowrishankar S, Kishan AG, Raman A. Non diabetic renal
disease in type 2 diabetes mellitus. Nephrology (Carlton). 2006;11:
533537.

51. Sorger K, Gessler U, Hubner FK, Kohler H, Schulz W, Stuhlinger W,

Thoenes GH, Thoenes W. Subtypes of acute postinfectious glomerulonephritis. Synopsis of clinical and pathological features. Clin Nephrol.
1982;17:114128.
52. Srivastava RN, Moudgil A, Bagga A, Vasudev AS, Bhuyan UN,
Sundraem KR. Crescentic glomerulonephritis in children: a review of 43
cases. Am J Nephrol. 1992;12:155161.
53. Srivastava T, Warady, Alon US. Pneumonia-associated acute glomerulonephritis. Clin Nephrol. 2002;57:175182.
54. Usmani SZ, Shahid Z, Wheeler D, Nasser K. A rare case of
postinfectious glomerulonephritis caused by pneumococcus in an adult
patient. J Nephrol. 2007;20:99102.
55. Vella J, Carmody M, Campbell E, Browne O, Doyle G, Donohoe J.
Glomerulonephritis after ventriculo-atrial shunt. QJM. 1995;88:911918.
56. Yum M, Maxwell DR, Hamburger R, Kleit SA. Primary glomerulonephritis complicating diabetic nephropathy: report of seven cases and
review of the literature. Hum Pathol. 1984;15:921927.
57. Zent R, Van Zyl Smit R, Duffield M, Cassidy MJ. Crescentic nephritis
at Groote Schuur Hospital, South Africanot a benign disease. Clin
Nephrol. 1994;42:2229.

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