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Acute NephritisAcute Nephritis
CSN VittalCSN VittalCSN VittalCSN Vittal
DefinitionDefinition
• An acute inflammation of renal glomerular An acute inflammation of renal glomerular paranchyma due to deposition of immune paranchyma due to deposition of immune complexes characterized by sudden onset ofcomplexes characterized by sudden onset of
oliguria, oliguria, hematuria, hematuria, hypertension and hypertension and edemaedema
IncidenceIncidence
• 2 to 4 % of pediatric admissions in India2 to 4 % of pediatric admissions in India
• 90 % of renal disease of childhood90 % of renal disease of childhood
EtiologyEtiology• Streptococcal infectionStreptococcal infection• Non streptococcalNon streptococcal
• Bacterial : Infective endocarditis, shunt nephritis, Bacterial : Infective endocarditis, shunt nephritis, typhoid, syphilis, S.pneumoniae, typhoid, syphilis, S.pneumoniae,
meningococcalmeningococcal
• Viral Viral : HBV, mumps, varicella, ECHO, coxsackie, : HBV, mumps, varicella, ECHO, coxsackie, measles, infective mononucleosis measles, infective mononucleosis
• AutoimmuneAutoimmune• Goodpastuer’s syndrome, HSP, SLE, IgA nephropathyGoodpastuer’s syndrome, HSP, SLE, IgA nephropathy
• MiscellaneousMiscellaneous• GBS, DPT vaccination, Irradiation to Wilms tumorGBS, DPT vaccination, Irradiation to Wilms tumor
PathologyPathology• Gross:Gross:
- Both kidneys enlarged- Both kidneys enlarged- Ischemic- Ischemic
• Microscopy:Microscopy:- Glomeruli enlarged, infiltrated by polymorphs- Glomeruli enlarged, infiltrated by polymorphs- Epithelial crescents- Epithelial crescents
• Immunofluorescence:Immunofluorescence:- Lumpy-bumpy deposits of IgG, antigen and C3- Lumpy-bumpy deposits of IgG, antigen and C3
• Electron microscopy:Electron microscopy:- Mesangial proliferation and mesangial matrix - Mesangial proliferation and mesangial matrix
deposition deposition- Lumps of immune complex depositions seen on - Lumps of immune complex depositions seen on
the epithelial side of GBM the epithelial side of GBM
The Clinical Spectrum of Renal Disease
Disease Category
(Most to Least
Severe)
Asymptomatic (e.g. Thin
basement membrane disease) (Least Severe)
Chronic progressive glomerulop
athy (e.g.
Diabetes nephropathy
)
Nephrotic syndrome
(e.g. Minimal change disease)
Nephritic syndrome (e.g. post-infectious
GN)
RPGN (Most
Severe)
Clinical Signs /
Symptoms
Microscopic hematuria
Insidious progressive loss of renal
function
Greater than 3.5
gm of protein in
24 hr urine
Hypertension, RBC casts,
Hematuria, Azotemia
Acute renal
failure + nephritic syndrom
e
AGN - PathophysiologyAGN - Pathophysiology
OliguriaOliguria1.1. Spasm of afferent arteriole (Spasm of afferent arteriole ( blood flow) blood flow)
2.2. Obliteration of lumen by mucosal edema & Obliteration of lumen by mucosal edema & cellular infiltrationcellular infiltration
3.3. Crescents causing obstruction Crescents causing obstruction
4.4. absorption of Na and water from renal absorption of Na and water from renal tubulestubules
AGN - PathophysiologyAGN - Pathophysiology
HypertensionHypertension1.1. absorption of Na and water from absorption of Na and water from
renal tubulesrenal tubules
2.2. sympathetic activitysympathetic activity
3.3. arterial spasmarterial spasm
4.4. cardiac outputcardiac output
AGN - PathophysiologyAGN - PathophysiologyOedemaOedema
1.1. Retention of Na and water from renal Retention of Na and water from renal
tubulestubules
2.2. Circulation of unknown antigen causing Circulation of unknown antigen causing
peripheral vasodilatation peripheral vasodilatation
AGN - PathophysiologyAGN - PathophysiologyHematuriaHematuria
• Presence of 5 or > RBC per mm3 fresh uncentrifuged midstream urine• >5 RBC per hpf in centrifuged specimen (of 10 ml, at 750 rpm for 5 min)• Macroscopic = > 25000 RBC / ml
1.1. Destruction and denudation of vesselsDestruction and denudation of vessels
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
- - EtiologyEtiology
• Streptococcal serotypes involvedStreptococcal serotypes involved• Pharyngitis :Pharyngitis :
• Types 1, 3, 4, Types 1, 3, 4, 1212, 25, 49, 25, 49
• PyodermaPyoderma• Types 2,47, Types 2,47, 4949, 55, 57, 60, 55, 57, 60
• Streptococcal antigens involved in immune response :Streptococcal antigens involved in immune response :• Zymogen precursor of exotoxinZymogen precursor of exotoxin
• Glutaraldehyde phosphate dehydrogenaseGlutaraldehyde phosphate dehydrogenase
Usually occurs 7-14 days after pharyngitis and 2 wks – 6 wks after skin infection
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
Age groupAge group2 – 12 yrs (Rare before 2 yrs)2 – 12 yrs (Rare before 2 yrs)
SexSexMale predominanceMale predominance
Socioeconomic groupSocioeconomic groupCommon in low socioeconomic groupCommon in low socioeconomic group
Seasonal variationSeasonal variationDuring winter and rainy season serotype 12 causes During winter and rainy season serotype 12 causes
Ac. pharyngitisAc. pharyngitis
During summer – serotype 49 causes skin infectionsDuring summer – serotype 49 causes skin infections
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
PathogenesisPathogenesis
Type III immunological reaction in which Type III immunological reaction in which
glomeruli are damaged due to deposition of glomeruli are damaged due to deposition of
IgG antibodyIgG antibody, , antigenantigen and and complement C3complement C3. .
Rarely C1q and C4 may be involvedRarely C1q and C4 may be involved
Post Streptococcal GlomerulonephritisPost Streptococcal GlomerulonephritisClinical FeaturesClinical Features
• Puffiness of face – more in the morningsPuffiness of face – more in the mornings• Edema feetEdema feet• Oliguria ( < 400 ml / mOliguria ( < 400 ml / m22))• Hematuria (cola coloured urine)Hematuria (cola coloured urine)• Breathlessness due to hypertensive heart failureBreathlessness due to hypertensive heart failure• FeverFever• HypertensionHypertension• Abdominal painAbdominal pain• Atypical presentations:Atypical presentations:
• Hypertensive encephalopathy – confusion, convulsions, etc.Hypertensive encephalopathy – confusion, convulsions, etc.• Pulomonary edema – due to CHFPulomonary edema – due to CHF• Acute renal failureAcute renal failure
HypertensionHypertensionValues AboveValues Above
80 / 4580 / 45 PretermPreterm
90 / 6090 / 60 Term NewbornTerm Newborn
120 / 75120 / 75 Up to 2 yearsUp to 2 years
130 / 80130 / 80 2 – 5 years2 – 5 years
135 / 85135 / 85 6 – 11 years6 – 11 years
140 / 90140 / 90 Older childrenOlder children
Post Streptococcal GlomerulonephritisPost Streptococcal GlomerulonephritisDiagnostic criteria of APSGNDiagnostic criteria of APSGN
At least 2 of the following criteria must be presentAt least 2 of the following criteria must be present
1.1. Positive throat or skin culture for Positive throat or skin culture for
streptococcusstreptococcus
2.2. Streptococcal products like Streptococcal products like
antistreptokinase, antihyalironidase, anti-antistreptokinase, antihyalironidase, anti-
Dnase B, ASO titre are elevated Dnase B, ASO titre are elevated (Anti – (Anti –
DNAse B is the single most specific test for DNAse B is the single most specific test for
Stereptococcal infection)Stereptococcal infection)
3. Hypocomplementemia3. HypocomplementemiaC3 and CH50 decreased with in 2 weeksC3 and CH50 decreased with in 2 weeks
Post Streptococcal GlomerulonephritisPost Streptococcal GlomerulonephritisInvestigations - For kidney injury :Investigations - For kidney injury :
Urine analysisUrine analysis• Proteinuria – non selectiveProteinuria – non selective• Hematuria : Hematuria :
- Macroscopic : - Macroscopic : Plenty of RBC & Plenty of RBC & RBC casts in urine RBC casts in urine
- Microscopic : - Microscopic : > 5 RBC / HPF in 10 ml> 5 RBC / HPF in 10 ml centrifuged urine centrifuged urine • HypocomplementemiaHypocomplementemia
Kidney function TestsKidney function Tests• Blood ureaBlood urea• S. creatinine (S. creatinine ( due to due to GFR) GFR)
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
Investigations - For Etiological FactoresInvestigations - For Etiological Factores
1.1. Culture of organisms in throat or skinCulture of organisms in throat or skin
2.2. Antistreptokinase, antihyalironidase – increasedAntistreptokinase, antihyalironidase – increased
3.3. ASO titer is increased if the disease is due to sero ASO titer is increased if the disease is due to sero
type 12 (throat infection) but not increased if the type 12 (throat infection) but not increased if the
disease is due to type 49 because subcutaneous lipids disease is due to type 49 because subcutaneous lipids
prevent the percolation of ASO titer in blood prevent the percolation of ASO titer in blood
4.4. Single most specific test : Anti DNAse – B Single most specific test : Anti DNAse – B
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
On light microscopy, usually see diffuse proliferative GN
Immunofluorescence Microscopy
Deposition of IgG and Deposition of IgG and C3C3
1. Mesangial
2. Starry sky (mesangial & capillary wall)
3. Garland (capillary loops)
Electron Microscopy
• large electron – dense immune deposits in subendothelial, subepithelial, and mesangial areas
Post Streptococcal GlomerulonephritisPost Streptococcal GlomerulonephritisCourse
• Renal Failure – less than 1 % in children, slightly higher in adults
• Resolution usually quick, • plasma Cr usually returns to previous levels by 3-4 weeks
• Hematuria resolves usually within 3-6 months,• Proteinuria falls at a slower rate• Some patients experience htn, recurrent proteinuria,
and renal insufficiency 10-40 yrs after• > 20% of adults may have some degree of persistent
proteinuria and or compromise of GFR for 1 year
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
ComplicationsComplications1. Hypertensive encephalopathy1. Hypertensive encephalopathy
Failure of autoregulatory system of the vessels of Failure of autoregulatory system of the vessels of brain due to acute rise of blood pressurebrain due to acute rise of blood pressure
• Altered sensorium, convulsions, etc,Altered sensorium, convulsions, etc,
2. Hypertensive heart failure2. Hypertensive heart failure
3. Hypocalcemia 3. Hypocalcemia
4. Hyperphosphatemia4. Hyperphosphatemia
5. Hyperkalemia5. Hyperkalemia
6. Acute renal failure6. Acute renal failure
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
Management PrinciplesManagement Principles
• Eliminate Strep. infection with antibiotics
• Supportive therapy
• Diuretics and antihypertensives to control bp and extra-cellular fluid volume
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
ManagementManagement
1. Infections control1. Infections control
2. Treatment of Hypertension2. Treatment of Hypertension
3. Treatment of Edema3. Treatment of Edema
4. Diet4. Diet
5. Fluid5. Fluid
6. Weight monitoring6. Weight monitoring
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
1. Infections:1. Infections: Drug of choice: Drug of choice: Penicilline Penicilline 4 – 8 Lakhs PPF for 10 days4 – 8 Lakhs PPF for 10 days
Management
1. Infections control2. Treatment of Hypertension
3. Treatment of Edema
4. Diet
5. Fluid
6. Weight monitoring
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
2. Hypertension:2. Hypertension: Mild cases – Mild cases –
managed with salt & managed with salt & water restriction.water restriction.
Drugs used : Atenelol, Drugs used : Atenelol, hydralazine, hydralazine, nifedipinenifedipine
Management
1. Infections control
2. Treatment of Hypertension
3. Treatment of Edema
4. Diet
5. Fluid
6. Weight monitoring
Management of Hypertensive EncephalopathyManagement of Hypertensive Encephalopathy
1. Intravenous Sodium Nitroprusside 1. Intravenous Sodium Nitroprusside [Arterial & venous vasodilator][Arterial & venous vasodilator]Dose : 0.3 µg / kg / min (max 10 µg / kg / min)Dose : 0.3 µg / kg / min (max 10 µg / kg / min)
2. Propranalol 2. Propranalol [[ 1 selective blocker] 1 selective blocker]Dose: 1-3 mg / kg / dose q 12 hDose: 1-3 mg / kg / dose q 12 h
3. Esmolol3. Esmolol [b 1 selective blocker][b 1 selective blocker]Dose: 130 – 300 µg / kg / min Dose: 130 – 300 µg / kg / min
4. Nifidepine 4. Nifidepine (Calcium channel blocker)(Calcium channel blocker)Dose : 0.5 mg / kg Sublingual repeated after 30 minDose : 0.5 mg / kg Sublingual repeated after 30 min
5. Amlodepine5. Amlodepine (Calcium channel blocker)(Calcium channel blocker)Dose : 0.1 to 0.6 mg / kg / d in 2-3 doses – OralDose : 0.1 to 0.6 mg / kg / d in 2-3 doses – Oral
6. 6. Labetelol Labetelol [Combined [Combined -adrenergic (-adrenergic (1 and 1 and 2) and 2) and -adrenergic -adrenergic blocker]blocker]
Dose : 0.2-1.0 mg/kg can be given as an IV bolus every Dose : 0.2-1.0 mg/kg can be given as an IV bolus every 10 min 10 min max bolus dose is 20 mg. max bolus dose is 20 mg.
Dosages of 0.25 - 3 mg / kg / hr by IV infusion - Dosages of 0.25 - 3 mg / kg / hr by IV infusion - recommended. recommended.
7. 7. HydralazineHydralazine : : [Direct arterial vasodilator with no effect on venous [Direct arterial vasodilator with no effect on venous circulation] circulation]
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
3. Edema & 5. Fluid 3. Edema & 5. Fluid IntakeIntake
• Urine out put should be accurately Urine out put should be accurately measured.measured.
• Fluid intake restricted to an Fluid intake restricted to an amount equal to insensible losses amount equal to insensible losses and 24 hr. urine outputand 24 hr. urine output
Diuretics :Diuretics :In presence of pulmonary In presence of pulmonary edema: edema:
Frusemide 2-3 mg / kg IV
Management
1. Infections control
2. Treatment of Hypertension
3. Treatment of Edema
4. Diet
5. Fluid6. Weight monitoring
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
3. Edema:3. Edema:• Urine out put should be accurately Urine out put should be accurately
measured.measured.
• Fluid intake restricted to an Fluid intake restricted to an amount equal to insensible losses amount equal to insensible losses and 24 hr. urine outputand 24 hr. urine output
Diuretics :Diuretics :
In presence of pulmonary In presence of pulmonary edema: edema:
Frusemide 2-3 mg / kg IV
Management
1. Infections control
2. Treatment of Hypertension
3. Treatment of Edema
4. Diet5. Fluid
6. Weight monitoring
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
6. Weight monitoring:6. Weight monitoring:• Child should be weighed dailyChild should be weighed daily
• In presence of severe oliguria, In presence of severe oliguria,
child should lose about 0.5 % of child should lose about 0.5 % of
body weight per day due to body weight per day due to
endogenous catabolismendogenous catabolism
• A gain in weight necessitates A gain in weight necessitates
reduction in fluid intakereduction in fluid intake
Management
1. Infections control
2. Treatment of Hypertension
3. Treatment of Edema
4. Diet
5. Fluid
6. Weight monitoring
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
Indications for Renal BiopsyIndications for Renal Biopsy
• Severe renal failure requiring dialysisSevere renal failure requiring dialysis• Hypertension – severeHypertension – severe• Unresolving Acute GN :Unresolving Acute GN :
- Massive proteinuria persisting > 4 wks - Massive proteinuria persisting > 4 wks
- Abnormal renal function (azotemia) - past 2 wks- Abnormal renal function (azotemia) - past 2 wks
- Low C3 for more than 8 wks- Low C3 for more than 8 wks
- Hypertension or hematuria past 3 wks- Hypertension or hematuria past 3 wks
- Urinary sedimentation abnormality persists >18 mo.- Urinary sedimentation abnormality persists >18 mo.• Features of systemic illnessFeatures of systemic illness
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
PreventionPrevention
Any streptococcal sore throat or skin infection should be Any streptococcal sore throat or skin infection should be treated withtreated with
• Benzyl Penicilline IM single dose Benzyl Penicilline IM single dose
6 Lakh IU - for < 6 yrs age6 Lakh IU - for < 6 yrs age
12 Lakh IU - for > 6 yrs age (or)12 Lakh IU - for > 6 yrs age (or)
• Oral Penicilline : 125 mg BID for 10 daysOral Penicilline : 125 mg BID for 10 days
• Ampicilline 100 mg / kg / d twice daily for 10 daysAmpicilline 100 mg / kg / d twice daily for 10 days
• Amoxicilline 50 mg / kg /d for 19 daysAmoxicilline 50 mg / kg /d for 19 days
There is no role for long term prophylaxis in acute nephritisThere is no role for long term prophylaxis in acute nephritis
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
Management of complications:Management of complications:• CCF• Hypertensive encephalopathy• ARF• Uremia• Acidosis• Hyperkalemia• Hyperphosphatemia• Hypocalcemia• Seizures
Post Streptococcal GlomerulonephritisPost Streptococcal Glomerulonephritis
PrognosisPrognosis
• 95% good prognosis95% good prognosis• Complement returns to normal within 3 wksComplement returns to normal within 3 wks• Microscopic hematuria persists for 1-2 wksMicroscopic hematuria persists for 1-2 wks• Hypertension returns to normal in 2-3 wksHypertension returns to normal in 2-3 wks
• 1-5 % Mortality1-5 % Mortality
• 1 – 5 % develop into Chronic GN, 1 – 5 % develop into Chronic GN, Chronic Renal FailureChronic Renal Failure
ARF (< 1ml / kg / hr) Management Protocol
• Fluid & Electrolyte :• Restrict to insensible losses + last day’s output
Insensible losses = 400 ml / m2 /day
Insensible losses – replaced by 10 % D/WLast day’s out put – 50% by 10% D/W and 50% by N. SalineGI Aspirates - by N. SalineIn severely over hydrated child – restrict all fluids
Newborn 30 ml / kg /d
Infant 25 ml / kg /d
1 – 5 yrs 20 ml / kg /d
5 – 10 yrs 15 ml / kg /d
> 10 yrs 10 ml / kg /d
ARF (< 1ml / kg / hr) Management Protocol
Hyperkalemia:
S. Potassium > 6 mEq / L• 10 % Calcium gluconate – 0.5 ml / kg IV dil . with
equal volume of dil. water and cardiac monitoring over 10 minutes.
• Soda bicarb 7.5 % = 3 mEq / IV ( 2-3 ml / kg) dil.with equal volume of distilled water or Insulin Glucose solution
• Insulin Glucose regimen ( if S.Pot > 7 mEq/L)• 50% glucose 1 ml with plaint insulin 1 unit / 5 G glucose
is given over 1 hr
ARF (< 1ml / kg / hr) Management Protocol
Acidosis:
Corrected slowly and carefully
For half correction of bicarbonate value :
Bicarbonate (mEq) = 0.3 X weight(kg) X (Desired HCO3 – Observed HCO3 )
Minimum of 15 mEq/L is considered desired serum HCO3
ARF (< 1ml / kg / hr) Management Protocol
Hyperphosphatemia:
When product of S. phosphorus and S. calcium reaches 70, calcium salts accumulate in urine
Restrict phosphorus rich foods ( all protein rich foods)
Phosphate binding calcium carbonate antacids – useful
ARF (< 1ml / kg / hr) Management Protocol
Hyponatremia: ( S. sodium < 120 mEq / L)
Corrected using normal saline
Or by
Hypertonic 3% Sodium Chloride (1 ml = 0.5 mEq)
Na (mEq) = [0.6 X Weight (kg) X (125 - S.Na) ]
Three Types of RPGN Based on Three Types of RPGN Based on Immunofluorescence PatternImmunofluorescence Pattern
TypeType PathogenesisPathogenesis Disease(s)Disease(s) PatternPattern StrengthStrength
II Anti-GBMAnti-GBMGoodpasture's Goodpasture's diseasedisease
Linear IgG, Weak linear Linear IgG, Weak linear C3C3
greater greater than 2+than 2+
IIIIImmune Immune complexcomplex
SLE, IgA SLE, IgA nephropathynephropathy
Granular Ig and C3 Granular Ig and C3 capillary loop/mesangiumcapillary loop/mesangium
greater greater than 2+than 2+
IIIIIIPauci-immune Pauci-immune or Unknownor Unknown
Wegener's Wegener's SyndromeSyndrome
Weak/Absent stainingWeak/Absent staining less than 2+less than 2+
Crescentic GN ( RPGN)
Focal Segemental Glomerulosclerosis
(FSGS)
Clumpy granular deposits IgA nephropathy
Goodpasteur syndrome
Lineal deposits
Glomerulonephritides associated with hypocomplimentemia
• Poststreptococcal
• Other infectious causes
• SBE
• Shunt nephritis
• SLE
• Membranoproliferative
Does the treatment of streptococcal skin or pharyngeal infection prevent APSGN?
• No study has ever demonstrated that treatment of impetigo or pharyngitis prevents renal complications in the index case.
• However, treatment lessens the likelihood of contagious spread to hosts who may be susceptible to renal complications
Some facts about APSGN
• Acute rheumatic fever does not occur after the skin infection
• About 80-85% of children with APSGN develop elevated ASO titers.
• Streptolysin O is bound to lipids in the skin so that the % of individual with streptococcal impetigo who develop +ve ASO titers is much lower. So normal ASO titer does not rule out recent strep. Infection
• Streptozyme test will be positive in > 95% of children with documented Strep. infection
ThanQ
- C.S.N.Vittal- C.S.N.Vittal- C.S.N.Vittal- C.S.N.Vittal
All my notes available at :
http://snipurl.com/2k691
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