Acute Nephritis in children-Is it always benign? : Acute Nephritis in children-Is it always benign? Susan Uthup MD DCH, DNB (Paed), D M , DNB (Nephro)
Assoc. Professor of Paediatric Nephrology
SAT Hospital
Govt. Medical College
Trivandrum
Introduction : Introduction Definition
Aetio pathogenesis
Clinical Features
Management
Case Scenarios
Discussion
Conclusions
Slide 5: Richard Bright 1927 Acute glomerulonephritis Abrupt onset
Hematuria
Oliguria
Oedema
Salt and water retention
Hypertension
Reduced GFR Prototype -Post infectious (eg. GABS)
The ‘Nephritic Syndrome ’ : The ‘Nephritic Syndrome ’ Acute, self limiting, reversible condition
Post Infectious – Epidemic / Sporadic
First presentation of chronic disease
IgA nephropathy
Membranoproliferative glomerulonephritis (MPGN)
Alport’s Syndrome
FSGS
Systemic Diseases
SLE and other chronic vasculitis
Acute Post infectious glomerulonephritis : Acute Post infectious glomerulonephritis Latent period : 2-3 weeks
Other infections …………….
Histologic pattern and clinical syndrome similar Deposition of immune complexes and complement in glomerular capillary bed
Nephritogenic strains : Nephritogenic strains M types 1,2, 4,12, 18, 25, 49, 55, 57, 60
Proposed mechanisms :
Molecular mimicry
Autoimmune mechanism
Polyclonal activation of B lymphocytes
Immune Complex mediated (insitu /in circulation)
Antigen load, Charge, Size
Effects of glomerular injury : Effects of glomerular injury Endothelium and subendothelial aspect of GBM
Recruitment of leukocytes ----inflammatory injury, Hematuria, proteinuria
Mesangium --Asymptomatic abnormalities of urinary sediment ; mild renal insufficiency
Parietal epithelial cells
crescent formation
(acute or subacute renal failure)
Nature of injury : Nature of injury Rapid, extensive, immune complex deposition
(poststreptococcal glomerulonephritis)
Complement activation
Leukocyte recruitment
Lysosomal enzyme release
Free radical generation
Purturbation of vascular tone & permeability
“Acute diffuse proliferative GN”
Acute renal failure
Nature of injury : Nature of injury Slow , but sustained IgA-immune complex formation (IgA nephropathy)
Less active inflammation
Relatively well maintained GFR
or
Slowly progressive renal insufficiency over decades
Post streptococcal GNClinical Features : Post streptococcal GNClinical Features Mild disease usual
Classically, overt nephritic syndrome . oliguric ARF
Gross hematuria (100% microscopic) Edema (80-90%)
Hypertension (60-80%)
Nephritic urinary sediment
dysmorphic RBCs, red cell casts, leukocytes
Proteinuria - Subnephrotic range
Nephrotic-range proteinuria- Uncommon Full recovery typically within weeks
INVESTIGATIONS : INVESTIGATIONS Urinalysis
Serum Creatinine
C3 decreased,C4 normal (complement level usually normal within 6-8 weeks)
ASO, anti-DNAse B
USS abdomen
Slide 14: Proliferative GN
Post infective PSGN- granular bumpy pattern of immune deposits on immunofluorescence
Immunofluorescence Microscopy : Immunofluorescence Microscopy Deposition of IgG and C3
Electron Microscopy : Electron Microscopy Large electron – dense immune deposits
subendothelial
subepithelial
mesangial
Treatment : Treatment Restriction of salt
Restriction of Fluid intake
Control of Hypertension with diuretics and anti hypertensives
Dialysis
Anuric renal failure
Symptomatic Azotemia
Diuretic resistant pulmonary oedema
Intractable Acidosis
Severe hyperkalemia
Indications for referral : Indications for referral Onset- Anuric renal failure,RPRF
Mixed nephritic-nephrotic presentation
Delayed recovery- including persistent
Hypertension (> 4 weeks)
Macroscopic hematuria (> 4 weeks)
Hypocomplimentaemia ( > 8 weeks)
Growth Failure
Family history of renal disease
.
Slide 19: Acute Glomerulo Nephritis
Case Scenarios
Case 1 : Case 1 5 yr Girl
Sudden onset Facial puffiness
Oliguria & Cola colored urine Generalized oedema
Headache
Preceeding infected skin lesion following trauma
No h/o skin rash, arthritis, bleeding manifestations or use of drugs
Physical Examination - Generalized Oedema, Hypertension
Growth Normal
On Evaluation : On Evaluation Urine coke colored
1-2 + proteinuria
Red blood cells, white blood cells, red cell and granular casts
Haemogram & Peripheral smear normal B. Urea 68-102-145mgm/dl
S. Creatinine 0.8—1.6—3-4 mgm/dl
S.Sodium / Potassium 128/5.8—132/6.4meq/L
ASO Positive
Serum Complement C3 – 0.3 mgm/dl (0.9- 1.2 mgm/dl) Sonography : Bulky kidneys with increased Echoes
Slide 23: RBC Cast
Acute Nephritic Syndrome - Possibilities : Acute Nephritic Syndrome - Possibilities Acute Post Streptococcal Glomerulonephritis
Primary glomerulonephritis – IgAN, FSGS
Henoch Schönlein Purpura
Rapidly progressive glomerulonephritis
Vasculitis like SLE
HUS
Acute interstitial Nephritis
Slide 26: Diffuse Endocapillary Exudative Proliferative GlomeruloNephritis
Rapidly progressive glomerulonephritis (RPGN) : Rapidly progressive glomerulonephritis (RPGN) crescemt = accumulation and proliferation of extracapillary cells.
The glomerular capillaries collapse and are bloodless, and fibrin can be identified within the capsule
it can stimulate proliferation of parietal epithelial cells
deposits of fibrin compress the glomerular capillary tuft
( GFR and destruction of glomerulus)
Slide 28: crescent
Types of Crescentic GN : Types of Crescentic GN Type 1: Anti-GBM antibody disease
Goodpasture’s syndrome
Type 2: Immune-complex
Lupus nephritis
Post-infectious
Mixed cryoglobulinemia
IgA
Type 3: Pauci-immune RPGN
Anti-neutrophil cytoplasmic antibodies (ANCA)
Wegner’s granulomatosis(cANCA); MPA; renal limited vasculitis(pANCA)
Case 2 : Case 2 14 year-old boy
Intermittent hematuria x 1 year
Intermittent proteinuria x 1 year
History of recurrent pharyngitis
Physical examination : Normotensive & Euvolemic
Is this Glomerular Bleeding? : Is this Glomerular Bleeding? Urinalysis: 3 + protein , RBC/HPF, Rare RBC cast
Many hyaline casts
Urine Culture sterile
Urine Spot PC ratio 1.8
Hb 11 gms, TC 7800 P42 L52 E6; ESR -12 mm/hr
Blood urea-52 mgm/dl. S.Creatinine-1 mgm/dl
Ultrasound abdomen: Normal Renal size, echogenicity CMD maintained
Slide 33: Serum Complement C3 -- - Normal
If C3 were reduced ??
Possibilities !!
Renal biopsy is indicated to make a histological diagnosis
What are the possibilities? : What are the possibilities? IgA Nephropathy
Henoch Schönlein Purpura (“allergic vasculitis”)
Alport Syndrome
Thin Basement Membrane Disease
Focal segmental glomerulosclerosis
Unlikely:
Membrano proliferative glomerulonephritis
Vasculitis-- Lupus Nephritis
IgA nephropathy (Bergers disease) : IgA nephropathy (Bergers disease) Etiology: - unknown
Syn Pharyngitic Nephritis -latent period 2-3 days
association with HLA (DQ, DP)
Mesangioproliferative GN with deposits of IgA, C3
T-lymphocytes produce levels of IL-2 (+ IR-2R)
They constantly stimulate production of IgA by
B-lymphocytes
Hereditary nephropathies : Hereditary nephropathies Alport syndrome
Hereditary nephritis with deafness
(X chromosome)
Pathogenesis: congenital defect of collag synthesis
GMB very slight or with more layers
GN focal (diffuse) proliferation with segmental sclerosis
hematuria, proteinuria or renal failure (males)
Case 3 : Case 3 15 yr girl
April 05 - Hematuria,Oedema,hypertension
Bilateral Knee Arthritis,Palpable purpura
October 05 – Recurrence of hematuria,Rash
March 07 - Persistent Proteinuria& microscopic hematuria
Growth normal
Euvolemic
BP 140/90 mm Hg
Investigations : Investigations Hb 12 gm;TC 6000
P46L53 E1
PLT 3.5 Lakhs
ESR 35mm/hr
Urine 3 + Protein,
Spot PC Ratio:2.2
RBC plenty
Pus Cells 20-40/hpf B.urea 27 gm/dl
S.Cr 0.6 mgm/dl
C3 Complement-150 mgm/dl Ultrasound abdomen: Normal Renal size, increased echogenicity
What are the possibilities? : What are the possibilities? Henoch Schönlein Purpura
IgA Nephropathy
Alport Syndrome
Thin Basement Membrane Disease
Focal segmental glomerulosclerosis
Unlikely:
Membrano proliferative glomerulonephritis
Vasculitis-- Lupus Nephritis
Henoch Schönlein Purpura systemic vasculitis affecting medium-sized vessels : Henoch Schönlein Purpura systemic vasculitis affecting medium-sized vessels Abdominal pain
Maculo-papular purpuric rash
Melena / intususception
Arthralgia/ Arthritis
Glomerulonephritis in 30% (similar to IgA N)
Clinical diagnosis
No specific diagnostic test
Case 4 : Case 4 15 yrs girl
2006 - Facial puffiness, Oliguria
Hematuria & renal Failure
C3 Complement- 80 mgm/dl
Treated as AGN
2007- Recurrence of hematuria
Renal failure
Asymptomatic in between
BP 110/70 mm Hg
Investigations : Investigations Hb 11 gm; TC 8000
P36 L63 E1
PLT 1.5 Lakhs
ESR 75mm/hr
Urine 2 + Protein
RBC plenty
Pus Cells 30-40/hpf B.urea 71 gm/dl
S.Cr 3.5 mgm/dl C3 Complement-30 mgm/dl Possibilites: MPGN, SLE----- Renal Biopsy Ultrasound abdomen: Normal Renal size increased echogenicity
Slide 45: Fibro cellular Crescents
Class IV Lupus Nephritis With Chronic Changes
Lupus Nephritis : Lupus Nephritis Many different tissues and organs involved in Lupus
Renal involvement - most significant in terms of outcome
Lupus NephritisWHO classification : Lupus NephritisWHO classification Minimal mesangial lupus nephritis (class I)
Mesangioproliferative lupus nephritis(class II)
Focal lupus nephritis (class III)
Diffuse lupus nephritis (class IV)
Membranous lupus nephritis (class V)
Advanced sclerosing lupus nephritis (class VI)
Slide 48: Crescentic Glomerulonephritis
Case 6 : Case 6 10 yr old boy
facial puffiness & Oliguria x 1 week
Pedal edema
Abdominal distension
No macrohematuria. No rash/joint pain Previously well child
Had pyoderma 3 weeks back No renal disease in family
Slide 50: Grade 1 PEM; 2º Stunting
Generalised oedema
Pyderma scar
Pallor
BP – 150/100 mmHg
CVS/RS/CNS : NAD
P/A : Ascites Physical Examination
Investigations : Investigations Hb 7.9 gm; TC:12,300; P84L16
ESR: 35mm/hr
Urine: Alb 2+
RBC 40-50/hpf
Urine c/s : sterile
Urea : 96 mg/dl;
S.Cr : 9 mg/dl
Na: 129 meq/l; K: 6.2 meq/l
ASO : 221U/L
C3 : 0.27mgm/dl Ca: 9 mg/dl
P:5.4 mg/dl
ALP: 182
S.Cholesterol:210 mg/dl
S.TP: 4.4gm/dl
S.Alb: 2.2gm/dl
SGOT/PT:30/15
HEMODIALYSIS via double lumen femoral cannula F3 dialyser : HEMODIALYSIS via double lumen femoral cannula F3 dialyser Child with
HEMATURIA
HYPERTENSION
RENAL FAILURE
HYPOCOMPLEMENTEMIA
HYPERKALEMIA
ANEMIA
GROWTH FAILURE
Slide 53: RAPIDLY PROGRESSIVE GLOMERULO NEPHRITIS
ACUTE POST INFECTIVE GLOMERULONEPHRITIS
BUT……..
PROBLEMS : PROBLEMS ACUTE…?
CHRONIC..?
ACUTE ON CHRONIC…?
Features of Underlying CRF : Features of Underlying CRF GROWTH FAILURE
ANEMIA
HYPERPHOSPHATEMIA
(Renal Osteodystrophy)
Confirmation…………
USG ABDOMEN : USG ABDOMEN B/L HYPERECHOIC
POOR CMD
Rt 5.7x2.5; Lt 5.8x2.8
MULTIPLE CYSTS IN BOTH KIDNEYS 7-8mm in the cortex Acute on Chronic Kidney Failure
Course of PIGN : Course of PIGN Typically Full recovery within weeks
Resolution quick. Plasma Cr usually returns to previous levels by 3-4 weeks
Hematuria resolves usually within 3-6 months
Irreversible Renal Failure rare – less than 1 % in children, slightly higher in adults
Some patients experience hypertension , recurrent proteinuria, and renal insufficiency 10-40 yrs after
More than 20% of adults have some degree of persistent proteinuria and or compromise of GFR at 1 year
Few Final Points : Few Final Points Correct and prompt diagnosis of AGN
Detect underlying renal or systemic Diseases early
Compliment the C3 always……
Distinguish acute from CKD
Follow Up always indicated as recovery may reveal the story better