Acute Nephritic Syndromes

1. ACUTE NEPHRITIC
SYNDROME
C H A I R P E R S O N : D R M A H A B A L E S H WA R M AY YA
S T U D E N T : D R R AV I K I R A N
N H R M C I M

2. INTRODUCTION
• Clinical presentation of nephritic syndrome includes
• Acute nephritic syndrome,
• Syndrome of rapidly progressive glomerulonephritis,
• Syndrome of chronic glomerulonephritis

3. INTRODUCTION

4. INTRODUCTION
Acute nephritic syndromes classically present with the
following:
• Hematuria
• Subnephrotic proteinuria (1- 2 g/24 h )
• Hypertension
• Fluid retention
• Red blood cell casts
• Pyuria
• Rise in serum creatinine
• Reduction in GFR

5. ACUTE NEPHRITIC SYNDROMES

6. ACUTE NEPHRITIC SYNDROMES

8. CAUSES ACCORDING TO AGE
CHILDREN AND
ADOLESCENTS
• Post-streptococcal
glomerulonephritis
• MPGN
• Cresentic GN
• IgA nephropathy
• Lupus Nephritis
• Henoch-Schönlein
purpura
ADULTS
• IgA Nephropathy
• Rapidly progressive
glomerulonephritis
• SLE or lupus nephritis
• ANCA associated
• Membranoproliferative GN
• Hepatitis B or C
• Infective endocarditis
• Abdominal abscesses
• Viral diseases such as
mononucleosis, measles,
mumps

9. INFECTIOUS CAUSES OF
ACUTE NEPHRITIS
• Infectious syndromes
• Specific bacterial
diseases
• Mycobacterial, rickettsial,
mycoplasmal, chlamydial,
and spirochetal diseases
• Fungal infections
• Viruses
• Parasitic infestations
NON-INFECTIOUS
CAUSES OF ACUTE
NEPHRITIS
• Immune mediated
glomerulonephritis
• Immune complex GN
• IgAN,HSP,LN…
• ANTI-GBM GN
• GPS,Anti-GBM
• ANCA associated GN
• MP,WG,CSS
Kanjanabuch, T. et al. Nat. Rev. Nephrol. 5, 259–269 (2009); doi:10.1038/nrneph.2009.44

10. SITE OF INJURY IN ACUTE
NEPHRITIC SYNDROME

11. APPROACH

12. CLINICAL APPROACH
(POST-INFECTIOUS)
On the background of Acute
Nephritis features….
• 5 and 12 years(90%) and >40(10%)
• boys > girls
• Pharyngitis(1-3)
• Impetigo(2-6)
• may be severe enough to appear as RPGN
• Constitutional symptoms - as many as 50%
of cases
IVDU
Cardiac
murmur
Dental
abscess.
Osteomy
elitis,dee
p seated
abscesse
s
Treated
hydroce
phalus
PSGN
Endocar
ditis
ShuntAbscess

13. IMMUNE MEDIATED
GLOMERULONEPHRITIS
IMMUNE COMPLEX
GN
ANTI-GBM GN
ANCA ASSOCIATED
GN

14. IMMUNE COMPLEX GN
On the background of
Acute Nephritis
features….
• 20s and 30s
• men >
women
• asymptoma
tic
microscopi
c hematuria
most often
seen in
adults
• Recurrent
synpharyng
itic gross
hematuria
• No vasulitis
• Asso with
systemic
diseases
• <20 years
of age(4-7)
• Macroscopi
c
haematuria
- time of
infections
• Purpuric
rash,
arthritis,
abdominal
pain
(Systemic
vasulitis)
• Young
women in 20
and 30s
• Arthralgia,
photosensiti
ve skin rash,
pleurisy, and
pericarditis
• 5 - 12 years
• boys > girls
• Acute Strept
infection(1-6
weeks
before
presentation
)
MPGN I
MPGN II
MPGN III
IgA
Nephropathy
HSP
Lupus
Nephritis
Acute PSGN MPGN

15. MPGN
• 20s; women > men
• Systemic symptoms
- most common
• Asso –
HepC,Cryogloulin,ne
oplasias
• Teenage;
women >
men
• Gaunt face
due to partial
Lypodystrop
hy
• 20s
• women
> men
MPGN I MPGN II MPGN III
• Middle age
• Abnormal
LFT(rarely
cirrhosis),
pupuric rash,
neuropathy,p
olyarthralgia,
leg ulcers
MPGN I with
Hep C

16. ANTI-GBM GN
On the background of
Acute Nephritis
features….
Young men(late
20s)
both sexes
(50s and 70s)
With lung
haemorrhage
GPS
20s:Young men;
50s and 60s:both
sexes
Without lung
haemorrhage
Anti-GBM GN

17. ANCA ASSOCIATED GN
With the background of
Acute Nephritis
features….
• 50s/60s
• men = women
• Weight loss,
malaise, LRT
symptoms,
arthritis,
palpable
purpura
• no Asthma
• 50s/60s
• men = women
• Weight loss,
malaise,
URT/LRT
symptoms,
arthritis,
palpable
purpura
• no Asthma
• 20-40
• Males>fema
les
• Asthma
• Neuropthy
Microscopic
Polyangitis
Wegeners
Granulomatosis
CSS

18. LABORATORY APPROACH

19. DARK URINE
DIPSTICK FOR
HEMENEGATIVE
DRUGS
FOOD DYES
MELANIN
POSITIVE
GROSS
HEMATURIA
MICROSCOPIC
HEMATURIA
TRAUMA
PRESENT
TRAUMA
ABSENT
IMAGING
OF
ABDOME
N AND
PELVIS
CYSTOS
COPY
PAINFUL PAINLESS
URINE
CALCIUM
URINE
CULTURE
RENAL
CALCULI
U.CA
FAMILIAL(Alp
orts)
HSP
HB ELECTRO
EUMORHIC
RBCs
DYSMORHI
C RBCs
U.CA
R/O
MEATAL
STENOSIS
FAMILY
SCREENIN
G(Thin
GBM)
W/U FOR
GLOMER
ULONEPH
RITIS
NO
RBCs
HB,MB

20. Photomicrograph of urine
sediment with a
red cell cast
Phase contrast micrograph
showing dysmorphic red cells
in urine sediment
Scanning electron micrograph
showing dysmorphic red cells
in urine sediment

23. INVESTIGATIONS

24. POST-INFECTIOUS GN
• Anti
streptolysin
titre
• anti-DNAse
B
• Throat swab
or skin swab
• 2D ECHO
• TEE
• USG
• X-ray
• VP shunt
evidence
PSGN Endocarditis ShuntAbscess
OTHER SPECIFIC
INVESTIGATIONS

25. IMMUNE COMPLEX GN
Glomerular immune complex
localisatIon with granular
capillary wall and/or
mesangeal staining
Raised serum
IgA in 50% of
cases,
Leucocytocl
astic
vasulitis
antinuclear
antibody/
anti-ds DNA,
anticardiolipi
n antibody
antistreptoly
sin titre
MPGN I
MPGN II
MPGN III
IgA
Nephropathy
HSP
Lupus
Nephritis
Acute PSGN MPGN
OTHER SPECIFIC
INVESTIGATIONS

26. MPGN
Low C4
(classical path
activation)
Low C3
(alternative path
activation),
C3 nephritic
factor
Dense deposits
Complement
receptors defect
MPGN I MPGN II MPGN III
Low C4, +ve
hepatitis C
serology,
hepatitis C RNA
on PCR, serum
cryoglobulins,
+ve
antinuclear
antibody/ +ve
Rh factor
MPGN I with
Hep C
OTHER SPECIFIC
INVESTIGATIONS

27. ANTI-GBM GN
Circulating Anti-GBM
antibodies with linear GBM
staining for IgG
• With evidence of
lung haemorrhage
GPS
• Without lung
haemorrhage
Anti-GBM GN
OTHER SPECIFIC
INVESTIGATIONS

28. ANCA ASSOCIATED GN
Circulating ANCA with
paucity of glomerular
immunoglobulin staining
P-ANCA(MPO)
Vasculitis with no
granuloma
No cavities
C-ANCA(RP3)
Granulomas
Cavitations
P-ANCA(MPO)
Eosinophilia
Granuloma
Microscopic
Polyangitis
Wegeners
Granulomatosis
CSS
OTHER SPECIFIC
INVESTIGATIONS

29. PIGN/IRGN

30. ACUTE POST-STREPTOCOCCAL
GLOMERULONEPHRITIS
• AGN that follows an infection with a nephritogenic strain
of group A beta hemolytic streptococci.
• The classic example of the acute nephritic syndrome.
• Incidence of clinically detectable glomerulonephritis
during an epidemic is up to 10% of children with
pharyngitis and 25% of children with impetigo
Nelson Textbook of Pediatrics, 7th Edition

31. STREPTOCOCCAL INFECTION OF THE
THROAT OR SKIN ( IMPETIGO)

32. EPIDEMIOLOGY
• Globally - incidence has decreased in the past three
decades.
• Throat (serotype 12) - cold weather months.
• Skin (serotype 49) - warm weather months.
BUT
• Most commonly – sporadic.
• Despite that, epidemics and clusters of cases – in some
poor or rural communities (© 2008 American Society of Nephrology)
• Peak incidence - age 5-12 y/o, uncommon <3y/o.
• Male : female ratio is 2 : 1.
Nelson Textbook of Pediatrics, 7th Edition

33. Clinical course
• Spontaneous improvement typically begins within 1 wk
• Resolution of edema in 5-10 days
• Hypertension in 3-4 wk
• Proteinuria -- normalize by 4-6 wk
• Acute phase resolves within 6-8 wk
• Urinalysis may be abnormal (persistent microscopic hematuria)
upto a year

34. ANTIBODIES TO STREPTOCOCCAL
ANTIGEN(S)
• Anti-streptolysin O titer (ASOT) >333 TOD Units
• COMMONLY elevated after a pharyngeal infection but
• RARELY increases after streptococcal skin infections
• Anti deoxyribonuclease (DNase) B antibodies
• best single antibody titer to document cutaneous streptococcal
infection
• Anti-hyaluronidase antibodies
• Anti-streptokinase antibodies

35. INDICATIONS FOR RENAL BIOPSY
• Severe acute renal failure requiring dialysis.
• Features suggesting non post-infectious AGN as the
cause of acute nephritis.
• Absence of the latent period between streptococcal
infection and acute glomerulonephritis
• Normal complement levels initially in early course
• Persistence of low C3 beyond 6-8 wks
• Delayed resolution
• Oliguria > 2 weeks
• Azotaemia > 3 weeks
• Gross haematuria > 3 weeks
• Persistent proteinuria > 6 months

36. LIGHT MICROSCOPE
(NOT SPECIFIC FOR POST STREPTOCOCCAL NEPHRITIS)
• Glomeruli -
enlarged,hypercel
lular.
• Diffuse mesangial
cell proliferation
• Increase in
mesangial matrix.
• PMNs - common
in glomeruli
• Crescents and
interstitial
inflammation

37. PSGN..
Immunofluorescence
microscopy
• Lumpy-bumpy deposits of
immunoglobulin
• Complement
• Glomerular basement
membrane (GBM)
• Mesangium
Electron microscopy
• Electron-dense deposits,
or "humps," on the
epithelial side of the GBM

40. MANAGEMENT
• Treatment is supportive
• control of hypertension, edema, and dialysis as
needed.
• Strict monitoring – I/O/weight/BP
• Penicillin V for 10 days to eliminate β - haemolytic
streptococcal infection (give erythromycin if penicillin is
contraindicated) patients
• Cohabitants(if culture positive for GAS)
• NOTE: Antibiotic therapy does not affect natural history
of glomerulonephritis

41. MANAGEMENT…
• Diet – no added salt to diet,Protein restriction is
unnecessary
• No role for immunosuppressive therapy(even in the
setting of crescents)
FOLLOW UP:
• Recheck serum complement at 6-8 wks.
• Check BP, renal function test and urinalysis every 1-3 month for
1 yr then yearly

42. COMPLICATIONS
• Hypertensive encephalopathy usually presenting with
seizures
• Pulmonary oedema (acute left ventricular failure)
• Acute renal failure

43. POOR PROGNOSIS INDICATED
IN…(PSGN)
• History of childhood PSGN
• Older age.
• History of massive proteinuria.
• History of Alcoholism or drug abuse.
• Underlying disease such as Diabetes, Cardiovascular and
liver disease.
• Persistent abnormal renal function.
• History of dialysis at presentation.
• Biopsy feature(including crescent)

44. OUTCOME
• Short term outcome: Excellent, mortality <0.5%.
• RPGN – 4.6%
• Long term outcome: 1.8% (1-3%) of children develop
chronic kidney disease
• Complete resolution  within 3–6 weeks
• Complete recovery
• >95% of children
• 60% of adult.

45. VARIANTS OF PIGN
• Staphylococcus associated GN.
• Associated with ventrilovascular shunt, IE .
• Some resemble IgA nephropathy.
• HBV associated GN.
• HIV associated GN such as HIVAN
• Other infection associated GN

46. GN ASSOCIATED WITH IE
• Incidence range from 22-78%.
• Highest among IV drug abusers
• Particularly in patients who:
• Remain untreated for an extended period of time
• Have negative blood cultures
• Have right-sided endocarditis (IVDU)
• Grossly, subcapsular hemorrhages with a "flea-bitten"
appearance
• Most typical finding is focal and segmental proliferative GN.
• Primary treatment is eradication of the infection with 4–6
weeks of antibiotics
• Prognosis is good.

47. SHUNT NEPHRITIS RELATED GN
• Immune mediated complex GN.
• Complication of chronic infection via ventriculovascular
shunts, common in treatment of hydrocephalus.
• In contrast to vascular shunt, VP shunt rarely
developed GN.
• Typical type I MPGN (deposit - mesangial and
subendothelial).
• Typical organisms are Staphylococcus spp

48. HCV INFECTION RELATED GN
• HCV frequently causes extrahepatic manifestation.
• Kidney involvement…
• Most common associated with type II
cryoglobulinemia.(1)
• Type I MPGN (Cryoglobulin deposits).
• Best long term prognostic indicator is HCV with SVR.
• RNA clearance from serum at least 6 month.
• Paucity of controlled study in HCV associated GN.
• Rituximab plus Peg-interferon a2b and Ribavarin show
good response in stabilized kidney function in
cryoglobulinemic vasculitis(2)
(1) Chapter 9; Infection-related GN. Kidney International Supplements (2012) 2, 200–208
(2) Saadoun D, Resche-Rigon M, Sene D et al. Rituximab combined with Peg-interferon-ribavirin in
refractory HCV -cryoglobulinaemia vasculitis. Ann Rheum Dis 2008; 67: 1431–1436.

49. HBV INFECTION RELATED GN
• Pattern of kidney involvement included.
• MN is the most common form, especially in children.
• Other such as MPGN, FSGS and IgAN.
• Exclude other cause of GN first.
• Prognosis…
• – In children high spontaneous remission.
• – In adult usually progressive, especially with abnormal
LFT and nephrotic syndrome, >50% progressing to ESRD.
• Treat HBV infection(Ente,Lami,Teno,Adefovir)
• Currently no data about efficacy of treatment in HBV-
related GN.

50. HIV RELATED GN
• Variety spectrum of kidney disease.
• HIVAN is the most common cause of CKD in HIV-1.
• APOL1 gene related.
• Typical collapsing FSGS on pathology.
• HAART is beneficial in both preservation and improvement in
kidney function.
• Not effective in other GN associated with HIV
infection.
• ACE-I may benefit in HIV with nephrotic syndrome

51. SCHISTOSOMAL NEPHROPATHY
• S.Mansoni and S.japonicum, blood fluke.
• Incidence is not well defined.
• Young adult males.
• Commonly seen eosinophiluria (65%) and
hypergammaglobilinemia (30%).
• Aware co-infection with salmonella,Especially in
Hepatosplenic involvement.
• Once established GN, currently no effective therapy.
• None of immunosuppresant recommended.
• Prevent by Praziquantel or Oxamiquine

52. FILARIAL NEPHROPATHY
• Loa loa, Onchocerca volvulus, W. bancrofti and B.
Malayi.
• Immune mediated from worm antigens.
• Urinary abnormalities have been reported 11-25%.
• Nephrotic syndrome 3-5%, concomitant with
polyarthritis and chorioretinitis. Especially in
lymphatic filariasis.
• Can induce diffuse GN and MPGN, MPGN, MND or
Sclerosing GN.
• Treat by Ivermectin or Diethylcarbamazine.

53. MALARIAL NEPHROPATHY
• P.Falciparum.
• May resulted in AKI or proliferative GN.
• P.Malariae.
• Variety of kidney disease especially MN or MPGN.
• Currently no RCT for evidence base treatment.
• Suggestion only appropriate anti-Malarial agent

54. IgA NEPHROPATHY
(IgAN)
• Berger's disease/Synpharyngitic glomerulonephritis
• MC type of GN worldwide
• Male preponderance
• Peak incidence in the 2nd and 3rd decades
• Recurrent painless gross hematuria.
• Preceded by (usually 1-3 days ) infections(URTI,GE).
• Defined by the presence of diffuse mesangial IgA
deposits often associated with mesangial
hypercellularity.

55. IgA NEPHROPATHY
• Deposits of IgA are also found in the glomerular
mesangium in a variety of systemic diseases, including:
• Chronic liver disease
• Crohn's disease
• Gastrointestinal adenocarcinoma
• Idiopathic interstitial pneumonia
• Dermatitis herpetiformis
• Mycosis fungoides
• Leprosy
• Ankylosing spondylitis

56. • IgA - polymeric forms
• Only IgA1 forms the nephritogenic deposits
• A genetic or acquired abnormality of immune
regulation leading to increased IgA synthesis in
response to respiratory or gastrointestinal exposure
to environmental agents
• HTN & renal insufficiency --- uncommon
• 30% to 40% have only microscopic hematuria, with
or without proteinuria
• 5% to 10% develop a typical acute nephritic
syndrome

57. PATHOGENESIS- SECONDARY IGA
NEPHROPATHY
• IgA nephropathy occurs with increased frequency
• gluten enteropathy (celiac disease), in whom intestinal
mucosal defects are well defined
• liver disease, in which there is defective hepatobiliary
clearance of IgA complexes (secondary IgA
nephropathy).
• Alternatively, there is evidence for qualitative alterations
in the IgA1 molecule itself

59. IgAN
• IgA nephropathy is typically an isolated renal disease,
similar IgA deposits are present in a systemic disorder of
children, Henoch-Schönlein purpura which has many
overlapping features with IgA nephropathy.
• In addition, secondary IgA nephropathy occurs in
patients with liver and intestinal diseases

60. IgAN..CLINICAL COURSE
• The hematuria typically lasts for several days and then
subsides, only to return every few months. The
subsequent course is highly variable
• Many patients maintain normal renal function for
decades.
• Slow progression to chronic renal failure occurs in 15%
to 40% of cases over a period of 20 years
• Recurrence of IgA deposits in transplanted kidneys is
frequent

61. IgAN… CLINICAL COURSE
• Clues to an increased risk of progression(loss of
renal function)
• Onset in old age
• Heavy proteinuria
• Hypertension
• Extent of glomerulosclerosis on biopsy
• Absence of episodes of macroscopic hematuria,
• male

62. IgA NEPHROPATHY
• Angiotensin-converting enzyme (ACE) inhibitors in
patients with proteinuria or declining renal function.
• When presenting as RPGN, patients typically receive:
• Steroids
• Cytotoxic agents
• Plasmapheresis

63. C3 GLOMERULONEPHRITIS

64. INTRODUCTION
• MPGN- not a diagnosis per se
• Rather a histopathologic pattern of injury
• See for potential underlying causes of injury
• Clinical classification
• Idiopathic or primary
• Secondary
• Primary MPGN – based on ultrastructural appearance and
location of electron-dense deposits
• Type I
• Type II
• Type III

65. • DDD was renamed MPGN2 in 1975
• Now considered inappropriate to refer to DDD as MPGN2
• Pathological pattern of MPGN is absent in the majority of cases
of DDD.

67. SUMMARY OF CLINICAL AND LABORATORY
FEATURES OF C3 GLOMERULOPATHIES

68. MANAGEMENT
• Predictors of outcome
• Renal dysfunction – Sr Cr, GFR
• Proteinuria
• DDD- older age at diagnosis - an independent
predictor of ESRD
• C3GN may have a more benign course than patients
with DDD

69. TREATMENT
• Targeted therapies have not proven to be universally
beneficial –
• Heterogeneity of the C3 glomerulopathies
• Control of alternative complement pathway activity
• Replacement of factor H - viable option
• Pts with genetic defects of inhibitory proteins of the
alternative complement pathway - replacement of factors

70. TREATMENT…
• Replacement
• Plasma exchange
• Pharmaceteucal preparation (not available at present)
• Replacement not successful in certain pts
• Mutant C3 convertase that is resistant to factor H Control
• Pts with an acquired antibody to an inhibitory
protein of the alternative pathway
• Immunosuppressive therapy
• Corticosteroids
• mycophenolate mofetil
• rituximab
• Eculizumab
• Humanized monoclonal antibody to C5
• Prevents the generation of the MAC

71. C3 GN VS DDD
• C3GN have a slightly better prognosis than do pts with
DDD
• DDD – progression to ESRD
• 25% after 5 years
• 50% after 10 years from diagnosis
• French cohort - C3 glomerulopathy
• ¼th of adult pts with C3GN progressed to ESRD over
10 years of f/u
• American cohort - C3GN
• No significant decline in renal function over a mean
follow-up of 26 months

72. REFERENCES
• Harrisons Principles of Internal Medicine – 19th Edition
• Brenner and Rector – The Kidney – 9th Edition
• Comprehensive Clinical Nephrology - John Feehally, Richard J.
Johnson, Jürgen Floege – 5th edition
• Nelson Textbook of Pediatrics, 7th Edition
• Acute glomerulonephritis ; C S Vinen, D B G Oliveira: Postgrad
Med J 2003;79:206–213
• An update on acute postinfectious glomerulonephritis
worldwide Talerngsak Kanjanabuch, Wipawee Kittikowit and
Somchai Eiam-Ong - Nat. Rev. Nephrol. 5, 259–269 (2009);
doi:10.1038/nrneph.2009.44
• INCIDENCE OF ACUTE POST STREPTOCOCCAL
GLOMERULONEPHRITIS IN CHILDREN
doi:10.1136/archdischild-2012-302724.1205

73. REFERENCES
• The Korean Society of Nephrology - New Classification of MPGN/Kidney
Res Clin Pract 33 (2014)171–173
http://dx.doi.org/10.1016/j.krcp.2014.10.005
• WG Couser and RJ Johnson: The etiology of glomerulonephritis: roles
of infection and autoimmunity - Kidney International (2014) 86, 905–914;
doi:10.1038/ki.2014.49
• Chapter 9; Infection-related GN. Kidney International Supplements
(2012) 2, 200–208
• Saadoun D, Resche-Rigon M, Sene D et al. Rituximab combined with
Peg-interferon-ribavirin in refractory HCV -cryoglobulinaemia vasculitis.
Ann Rheum Dis 2008; 67: 1431–1436

74. THANK YOU