Transcript Post-infectious glomerulonephritis

Post-infectious glomerulonephritis
Stephen Marks
Consultant Paediatric Nephrologist
Great Ormond Street Hospital for Children and
UCL Institute of Child Health, London, UK.
Nephrology for the General Paediatrician, Manchester
Friday 22 June 2012
Summary
• Case presentation
• Causes
• Management
• Prognosis
Case presentation
• 15-year old Afro-Caribbean boy
– 1 week history of abdominal, leg and facial swelling with
increasing shortness of breath
– he and his siblings have had a few ?viral infections with sore
throat over the last 3 winter months
– no rash but reduced oral intake over last 24 hours with oliguria
• On examination
–
–
–
–
–
unwell with weight on 25th centile and height on 2nd centile
capillary refill time of 2 seconds with palpable peripheral pulses
prominent apex beat, BP = 152/94 mmHg
tachypnoeic with lung crepitations in all areas
generalised oedema and ascites
Investigations
•
•
•
•
Hb
12.0 g/dl
WCC
12.3 x 109/l
Platelets 325 x 109/l
Sickle screen
-ve
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•
•
•
•
•
•
•
•
•
Sodium 130 mmol/l
Potassium 7.2 mmol/l
Chloride 108 mmol/l
tCO2
14 mmol/l
Urea
24.8 mmol/l
Creatinine 258 µmol/l
• Urinary dipstick
• Calcium
• Albumin
1.8mmol/l
24g/l
Phosphate 1.6 mmol/l
ALP
160 U/l
ALT
24 U/l
Bilirubin 12 µmol/l
– proteinuria ++++
– haematuria ++
• CXR
– normal heart size
– pulmonary oedema
• Renal ultrasound
– two big echobright kidneys
Question (a)
• Which two of the following are the best
descriptions of his clinical condition ?
A.
B.
C.
D.
E.
F.
G.
H.
Acute renal failure / acute kidney injury
Acute on chronic renal failure
Chronic renal failure or chronic kidney disease
End-stage renal failure
Neither nephritic nor nephrotic syndrome
Nephritic syndrome (but not nephrotic syndrome)
Nephrotic syndrome (but not nephritic syndrome)
Nephritic and nephrotic syndrome
Question (b)
• In which range is this patient’s corrected
calcium in ?
A. 1.71 - 1.8mmol/l
B. 1.81 - 1.9mmol/l
C. 1.91 - 2.0mmol/l
D. 2.01 - 2.1mmol/l
E. 2.11 - 2.2mmol/l
Question (c)
•
Which of the following would not be part of an
effective management plan for his
hyperkalaemia ?
A.
B.
C.
D.
E.
F.
G.
H.
Calcium carbonate
Calcium gluconate
Calcium resonium
Cardiac monitor
Furosemide
Insulin and dextrose infusion
Salbutamol
Sodium bicarbonate
Question (d)
•
How would you treat his hypertension ?
A.
B.
C.
D.
E.
F.
G.
H.
I.
J.
Intravenous 4.5% albumin infusion
Intravenous 20% albumin infusion and furosemide
Intravenous furosemide
Intravenous labetalol
Low salt diet
Oral amlodipine
Oral atenolol
Oral enalapril
Oral furosemide
Oral nifedipine
Question (e)
•
Despite initial fluid and medical management, he
becomes anuric for 48 hours and his plasma
creatinine increases to 512µmol/l
•
What one investigation would you do to help make
the diagnosis ?
A.
B.
C.
D.
E.
F.
G.
H.
ANA and anti-dsDNA
Anti-GBM antibody
Anti-streptolysin O and anti-DNAase B titres
Auto-immune screen
Blood film
C3, C4 and auto-antibody screen
Immunoglobulin levels
Renal biopsy
Question (f)
•
What is the most likely diagnosis ?
A.
B.
C.
D.
E.
Haemolytic uraemic syndrome
Minimal change nephrotic syndrome
Post-infectious glomerulonephritis
Renal venous thrombosis
Sickle nephropathy
Question (a)
• Which two of the following are the best
descriptions of his clinical condition ?
A.
B.
C.
D.
E.
F.
G.
H.
Acute renal failure / acute kidney injury
Acute on chronic renal failure
Chronic renal failure or chronic kidney disease
End-stage renal failure
Neither nephritic nor nephrotic syndrome
Nephritic syndrome (but not nephrotic syndrome)
Nephrotic syndrome (but not nephritic syndrome)
Nephritic and nephrotic syndrome
Question (a)
• Which two of the following are the best
descriptions of his clinical condition ?
A.
B.
C.
D.
E.
F.
G.
H.
Acute renal failure / acute kidney injury
Acute on chronic renal failure
Chronic renal failure or chronic kidney disease
End-stage renal failure
Neither nephritic nor nephrotic syndrome
Nephritic syndrome (but not nephrotic syndrome)
Nephrotic syndrome (but not nephritic syndrome)
Nephritic and nephrotic syndrome
Question (b)
• In which range is this patient’s corrected
calcium in ?
A. 1.71 - 1.8mmol/l
B. 1.81 - 1.9mmol/l
C. 1.91 - 2.0mmol/l
D. 2.01 - 2.1mmol/l
E. 2.11 - 2.2mmol/l
Question (b)
• In which range is this patient’s corrected
calcium in ?
A. 1.71 - 1.8mmol/l
B. 1.81 - 1.9mmol/l
C. 1.91 - 2.0mmol/l
D. 2.01 - 2.1mmol/l
E. 2.11 - 2.2mmol/l
Corrected calcium
• How do you calculate corrected calcium from
total calcium result ?
• Corrected calcium = Total calcium +
[(40 - Patient’s albumin (g/l)) x 0.025]
• Some sources use correction factor of 0.02
instead of 0.025
Corrected calcium
• Corrected calcium = Total calcium +
[(40 - Patient’s albumin (g/l)) x 0.025]
• For this case, corrected calcium
= 1.8mmol/l + [(40 - 24) x 0.025]
= 1.8mmol/l + (16 x 0.025)
= 1.8mmol/l + 0.4
= 2.2mmol/l
Question (c)
•
Which of the following would not be part of an
effective management plan for his
hyperkalaemia ?
A.
B.
C.
D.
E.
F.
G.
H.
Calcium carbonate
Calcium gluconate
Calcium resonium
Cardiac monitor
Furosemide
Insulin and dextrose infusion
Salbutamol
Sodium bicarbonate
Question (c)
•
Which of the following would not be part of an
effective management plan for his
hyperkalaemia ?
A.
B.
C.
D.
E.
F.
G.
H.
Calcium carbonate
Calcium gluconate
Calcium resonium
Cardiac monitor
Furosemide
Insulin and dextrose infusion
Salbutamol
Sodium bicarbonate
Question (d)
•
How would you treat his hypertension ?
A.
B.
C.
D.
E.
F.
G.
H.
I.
J.
Intravenous 4.5% albumin infusion
Intravenous 20% albumin infusion and furosemide
Intravenous furosemide
Intravenous labetalol
Low salt diet
Oral amlodipine
Oral atenolol
Oral enalapril
Oral furosemide
Oral nifedipine
Question (d)
•
How would you treat his hypertension ?
A.
B.
C.
D.
E.
F.
G.
H.
I.
J.
Intravenous 4.5% albumin infusion
Intravenous 20% albumin infusion and furosemide
Intravenous furosemide
Intravenous labetalol
Low salt diet
Oral amlodipine
Oral atenolol
Oral enalapril
Oral furosemide
Oral nifedipine
Question (e)
•
Despite initial fluid and medical management, he
becomes anuric for 48 hours and his plasma
creatinine increases to 512µmol/l
•
What one investigation would you do to help make
the diagnosis ?
A.
B.
C.
D.
E.
F.
G.
H.
ANA and anti-dsDNA
Anti-GBM antibody
Anti-streptolysin O and anti-DNAase B titres
Auto-immune screen
Blood film
C3, C4 and auto-antibody screen
Immunoglobulin levels
Renal biopsy
Question (e)
•
Despite initial fluid and medical management, he
becomes anuric for 48 hours and his plasma
creatinine increases to 512µmol/l
•
What one investigation would you do to help make
the diagnosis ?
A.
B.
C.
D.
E.
F.
G.
H.
ANA and anti-dsDNA
Anti-GBM antibody
Anti-streptolysin O and anti-DNAase B titres
Auto-immune screen
Blood film
C3, C4 and auto-antibody screen
Immunoglobulin levels
Renal biopsy
Question (f)
•
What is the most likely diagnosis ?
A.
B.
C.
D.
E.
Haemolytic uraemic syndrome
Minimal change nephrotic syndrome
Post-infectious glomerulonephritis
Renal venous thrombosis
Sickle nephropathy
Question (f)
•
What is the most likely diagnosis ?
A.
B.
C.
D.
E.
Haemolytic uraemic syndrome
Minimal change nephrotic syndrome
Post-infectious glomerulonephritis
Renal venous thrombosis
Sickle nephropathy
Hypocomplementaemia
• Immune-complex mediated disorders
– infective endocarditis
– shunt nephritis
• activation of the complement pathway and resulting
hypocomplementaemia
• MPGN (but not FSGS) associated with low C3
• RPGN is a clinical diagnosis and is not
necessarily hypocomplementaemic
Post-infectious glomerulonephritis - 1
• Post-streptococcal GN
– prototype for bacterial infection-related GN (PIGN)
with antecedent pharyngeal (7 - 15 days) or
cutaneous infection (eg. impetigo; 4 -6 weeks)
– caused by nephritogenic strain of Streptococci
• NATURE OF NEPHRITOGENIC ANTIGEN DEBATED
– <50% complete remission on long follow-up of
immunocompromised adults with atypical PIGN
• Moroni G, Ponticelli C (2009)
Post-infectious glomerulonephritis - 2
• Incidence and spectrum changing
– epidemic form declined in industrialised countries
• post-streptococcal glomerulonephritis = 28 - 47% of acute GN
• Staph aureus / epidermidis =
12 - 24%
• Gram negative bacteria =
10 - 22%
– others
• inc. bacterial endocarditis, shunt infections, atypical PIGN
– acute endocapillary glomerulonephritis with mesangial
and capillary granular immune deposition
• Montseny JJ et al (1995) Medicine (Baltimore)
• Moroni G et al (2002) Nephrol Dial Transplant
• Nasr SH et al (2008) Medicine (Baltimore)
Percutaneous renal biopsy
Clinical course of PIGN
• Acute GN < 2 weeks
• Massive proteinuria in <4% of PSGN children
• Severe end of spectrum with RPGN
– histopathologically crescentic GN
• Resolution of hypocomplementaemia (C3)
– by 8 - 10 weeks
Post-infectious glomerulonephritis
• The indications for renal biopsy are
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–
–
–
severe renal dysfunction at presentation
rapidly progressive acute renal failure
atypical presentation
delayed recovery
• macroscopic haematuria for >1 month
• low C3 levels for >6 months
• heavy proteinuria for > 6 months
• Note that microscopic haematuria can persist
for years following the acute episode
Causes of PIGN
Treatment of PIGN
• Supportive treatment
– management of fluids and electrolytes
– acute (and chronic) treatment of hypertension, oedema,
congestive cardiac failure and proteinuria
• Specific treatment
– antibiotics are unhelpful for reversing GN as established
glomerular lesions induced by immune complexes
– penicillin (or erythromycin if allergic)
• to resolve well-documented streptococcal infection
• to prevent spread of nephritogenic streptococcus in contacts
– no RCT but intravenous methylprednisolone if extensive
glomerular crescents and RPGN
• based on extrapoloation from other causes of RPGN
Mixed nephritic and nephrotic
Nephritic syndrome
Nephrotic syndrome
Mixed nephritic and nephrotic
Nephritic syndrome
• Haematuria
• Proteinuria
• Oliguria
• Hypertension
Nephrotic syndrome
Mixed nephritic and nephrotic
Nephritic syndrome
Nephrotic syndrome
• Haematuria
• Proteinuria
• Proteinuria
– > 40mg/m2/hour
– > 1g/m2/day
• Hypoalbuminaemia
• Oliguria
• Hypertension
– < 25g/l
• Oedema
• (Hyperlipidaemia)
Mixed nephritic and nephrotic
Nephritic syndrome
Nephrotic syndrome
• Commonest cause
• Commonest cause
– PIGN / PSGN or
post-infectious
glomerulonephritis
– MCD / MCNS or
minimal change
nephrotic syndrome
Mixed nephritic and nephrotic
Nephritic syndrome
Nephrotic syndrome
• Commonest cause
• Commonest cause
– PIGN / PSGN or
post-infectious
glomerulonephritis
– MCD / MCNS or
minimal change
nephrotic syndrome
Commonest cause of mixed
nephritic and nephrotic syndrome
is post-infectious GN
Red blood cell cast
• Prerenal
• Renal
• Postrenal
Clinical features - Examination
• State of patient
• Routine observations
– temperature, HR, SBP, RR, SaO2, AVPU (GCS)
– core-peripheral temperature
• Serial plot of weights, heights and OFC
• State of hydration
– peripheral perfusion, JVP, oedema
• Signs of cardiac failure
• Clinical clues of multi-system disease
– rash, arthropathy, arthritis, oral lesions
• Palpable kidneys or bladder or masses
Investigations – Blood tests (1)
•
•
•
•
Full blood count, blood film and ESR
Coagulation screen
Cross-match
Serum electrolytes
– U&Es, Cl, CO2, urea, creatinine, glucose
– LFTs, CK, urate, bone profile
– Ca, Mg, PO4, ALP, albumin
• Blood culture and CRP
Investigations – Blood tests (2)
• Complement assays
– C3, C4 and C3 nephritic factor
• Immunoglobulins including IgA
• ASOT and antiDNAase B
• ANA, dsDNA, qDNA, ENA, ANCA, ACIgM/G
• Autoimmune profile and anti-GBM Ab
Investigations – Urine tests
•
•
•
•
Urinalysis
Urine M,C&S
Urine electrolytes
Fractional excretion of sodium (FENa)
=
UNa x PCr
—————
PNa x UCr
Urine electrolytes in ARF
• Only on patients NOT on diuretics
Test
Na
Urea
U:P urea
U:P Cr
Sediment
Prerenal
<20
>250
>20
>20
Nil
Renal
>20
<150
<10
<15
? Sediment
Investigations – Other tests
• Renal ultrasound scan
– bilateral echogenic kidneys
• Percutaneous renal biopsy
– confirm PIGN
– exclude MPGN
– consider crescentic GN
Investigations – Ongoing tests
• U&Es, CO2 and creatinine
– frequency determined by clinical picture and may
be appropriate to perform up to every 6 hours
• Ca, PO4, Mg, albumin, ALP (at least daily)
• FBC daily
• Urinalysis daily
• Urine electrolytes daily (unless on diuretics)
Fluid balance
HYDRATION
STATUS
CLINICAL
FEATURES
INITIAL
MANAGEMENT *
Dehydrated
Tachycardic, cool peripheries,
prolonged CRT, dry mucous
membranes, sunken eyes,
UNa <10 (<20 in neonates),
FENa < 1% (< 2.5% in
neonates)
Fluid challenge 10-20 ml/kg
normal saline over 1 hour
Euvolaemic
Overloaded
Fluid challenge 10-20 ml/kg
normal saline over 1 hour,
consider furosemide up to 5
mg/kg if no urine response
Tachycardic, gallop rhythm,
elevated JVP, oedema,
hypertension
Furosemide 5 mg/kg if fluid
overload is severe; dialysis if
no response to furosemide
Patient Progress - 1
• Further fluid boluses of crystalloid or colloid
+/- furosemide as indicated by clinical state of
hydration and urine output
• Monitoring
–
–
–
–
daily or twice daily weights
accurate input-output recording
at least 4 hourly BP
at least 4 hourly monitoring of peripheral-core
temperature gradient
Patient Progress - 2
• Ongoing fluid management
– initially simplest plan is to give insensible losses
(400 ml/m2/day or 30 ml/kg/day) and replace UO
• GIVE 100% URINE OUTPUT (UO) IF
EUVOLAEMIC
• RESTRICT TO 50-75% UO IF OVERLOADED
• MODIFIED TO FLUID RESTRICTION IF ON
DIALYSIS OR URINE OUTPUT ESTABLISHED
• In polyuric recovery phase
– replace urine output with insensible losses for 24
hours, then set fluid target if renal function
continuing to improve
Multidisciplinary team
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•
•
•
•
•
•
Doctors
Nurses
Pharmacists
Dietitians
Play therapists
Social worker
Psychosocial team
Clinical problems
•
How would you manage
1.
2.
3.
4.
5.
6.
7.
Hyperkalaemia
Hyponatraemia
Hypernatraemia
Hypocalcaemia
Hyperphosphataemia
Acidosis
Hypertension ?
Treatment - 1
•
Hyperkalaemia
–
–
•
Hyponatraemia 2y to fluid overload
–
•
fluid restriction; RRT; hypertonic saline (Na<120)
Hypernatraemia 2y to sodium retention
–
•
cardiac monitor; salbutamol; NaHCO3;
furosemide; Ca resonium and insulin:dextrose
furosemide; dialysis (if oliguria)
Hypocalcaemia is multifactorial
–
–
1-alphahydroxycholecalciferol
calcium supplements
Treatment - 2
•
Hyperphosphataemia
–
–
•
Acidosis
–
•
dietary phosphate restriction
phosphate binders
sodium bicarbonate therapy
Hypertension 2y to fluid overload or
alteration in vascular tone
–
–
–
diuretics; medical management;
dialysis if failure to respond to diuretics
dialysis if pulmonary oedema and oliguria
Nutritional aspects of AKI
• AKI associated with catabolic state and
malnutrition can develop rapidly
• Malnutrition delays AKI recovery and
anecdotal evidence that good nutrition
improves outcome
• Dietetic review for children with AKI to
prescribe low K, low PO4 diet
• Aim for at least maintenance calorie intake
and protein intake of 0.6g/kg
• Start nutritional feeds orally or via NG tube to
minimise catabolism & uraemia: IF NOT TPN
Drug dosages in ARF
• For the purposes of correcting drug doses
according to GFR
– assume GFR < 20mls/min/1.73m2 before recovery
– change of GFR is important and drug doses may
need to be revised regularly
• Many drugs require decreased doses or
prolonged dosage interval in renal failure
– consult formulary and pharmacist for advice
• Best to avoid known nephrotoxic drugs
Indications for referral to nephrology for
renal replacement therapy
• What are the indications ?
Indications for referral to nephrology for
renal replacement therapy
• Hyperkalaemia > 6.5 mmol/l
• Severe fluid overload with pulmonary oedema
which is resistant to diuretics
• Uraemia > 40 mmol/l
• Other conditions
– multi-system failure
– anticipation of prolonged oliguria
Prognosis
• Favourable outcome with spontaneous
recovery within a few weeks
– <1% of patients develop ESRF at 15 years
– 20% mortality in elderly who are more
prone to develop proteinuria requiring ACEi
and/or ARB
• Rodriguez-Iturbe B et al (2008) J Am Soc Nephrol
Causes and mortality of AKI in India
Sinha R et al
(2009) NDT
Research recommentations
• An RCT is needed to evaluate the
treatment of crescentic
poststreptococcal GN with
corticosteroids
• Research is needed to determine the
nature of the streptococcal antigen, as a
basis for developing
immunoprophylactic therapy
Take home messages…
• Monitoring changes in clinical status is
paramount
– observations
– blood and urine test results
• Most crucial element to management is
fluid balance
Any questions ?