Post-infectious glomerulonephritis
Stephen MarksConsultant Paediatric Nephrologist
Great Ormond Street Hospital for Children and UCL Institute of Child Health, London, UK.
Nephrology for the General Paediatrician, ManchesterFriday 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
• 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
• Calcium 1.8mmol/l• Albumin 24g/l
• Phosphate 1.6 mmol/l• ALP 160 U/l• ALT 24 U/l• Bilirubin 12 µmol/l
• Urinary dipstick– 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. Acute renal failure / acute kidney injuryB. Acute on chronic renal failureC. Chronic renal failure or chronic kidney diseaseD. End-stage renal failureE. Neither nephritic nor nephrotic syndromeF. Nephritic syndrome (but not nephrotic
syndrome)G. Nephrotic syndrome (but not nephritic
syndrome)H. 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. Calcium carbonateB. Calcium gluconateC. Calcium resoniumD. Cardiac monitorE. FurosemideF. Insulin and dextrose infusionG. SalbutamolH. Sodium bicarbonate
Question (d)
• How would you treat his hypertension ?
A. Intravenous 4.5% albumin infusion B. Intravenous 20% albumin infusion and furosemideC. Intravenous furosemideD. Intravenous labetalolE. Low salt dietF. Oral amlodipineG. Oral atenololH. Oral enalaprilI. Oral furosemideJ. 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. ANA and anti-dsDNAB. Anti-GBM antibodyC. Anti-streptolysin O and anti-DNAase B titresD. Auto-immune screenE. Blood filmF. C3, C4 and auto-antibody screenG. Immunoglobulin levelsH. Renal biopsy
Question (f)
• What is the most likely diagnosis ?
A. Haemolytic uraemic syndrome
B. Minimal change nephrotic syndrome
C. Post-infectious glomerulonephritis
D. Renal venous thrombosis
E. Sickle nephropathy
Question (a)
• Which two of the following are the best descriptions of his clinical condition ?
A. Acute renal failure / acute kidney injuryB. Acute on chronic renal failureC. Chronic renal failure or chronic kidney diseaseD. End-stage renal failureE. Neither nephritic nor nephrotic syndromeF. Nephritic syndrome (but not nephrotic
syndrome)G. Nephrotic syndrome (but not nephritic
syndrome)H. Nephritic and nephrotic syndrome
Question (a)
• Which two of the following are the best descriptions of his clinical condition ?
A. Acute renal failure / acute kidney injuryB. Acute on chronic renal failureC. Chronic renal failure or chronic kidney diseaseD. End-stage renal failureE. Neither nephritic nor nephrotic syndromeF. Nephritic syndrome (but not nephrotic
syndrome)G. Nephrotic syndrome (but not nephritic
syndrome)H. 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. Calcium carbonateB. Calcium gluconateC. Calcium resoniumD. Cardiac monitorE. FurosemideF. Insulin and dextrose infusionG. SalbutamolH. Sodium bicarbonate
Question (c)
• Which of the following would not be part of an effective management plan for his hyperkalaemia ?
A. Calcium carbonateB. Calcium gluconateC. Calcium resoniumD. Cardiac monitorE. FurosemideF. Insulin and dextrose infusionG. SalbutamolH. Sodium bicarbonate
Question (d)
• How would you treat his hypertension ?
A. Intravenous 4.5% albumin infusion B. Intravenous 20% albumin infusion and furosemideC. Intravenous furosemideD. Intravenous labetalolE. Low salt dietF. Oral amlodipineG. Oral atenololH. Oral enalaprilI. Oral furosemideJ. Oral nifedipine
Question (d)
• How would you treat his hypertension ?
A. Intravenous 4.5% albumin infusion B. Intravenous 20% albumin infusion and furosemideC. Intravenous furosemideD. Intravenous labetalolE. Low salt dietF. Oral amlodipineG. Oral atenololH. Oral enalaprilI. Oral furosemideJ. 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. ANA and anti-dsDNAB. Anti-GBM antibodyC. Anti-streptolysin O and anti-DNAase B titresD. Auto-immune screenE. Blood filmF. C3, C4 and auto-antibody screenG. Immunoglobulin levelsH. 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. ANA and anti-dsDNAB. Anti-GBM antibodyC. Anti-streptolysin O and anti-DNAase B titresD. Auto-immune screenE. Blood filmF. C3, C4 and auto-antibody screenG. Immunoglobulin levelsH. Renal biopsy
Question (f)
• What is the most likely diagnosis ?
A. Haemolytic uraemic syndrome
B. Minimal change nephrotic syndrome
C. Post-infectious glomerulonephritis
D. Renal venous thrombosis
E. Sickle nephropathy
Question (f)
• What is the most likely diagnosis ?
A. Haemolytic uraemic syndrome
B. Minimal change nephrotic syndrome
C. Post-infectious glomerulonephritis
D. Renal venous thrombosis
E. 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– 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
• Haematuria
• Proteinuria
• Oliguria
• Hypertension
Nephrotic syndrome
• Proteinuria– > 40mg/m2/hour– > 1g/m2/day
• Hypoalbuminaemia– < 25g/l
• Oedema• (Hyperlipidaemia)
Mixed nephritic and nephrotic
Nephritic syndrome
• Commonest cause– PIGN / PSGN or
post-infectious glomerulonephritis
Nephrotic syndrome
• Commonest cause– MCD / MCNS or
minimal change nephrotic syndrome
Mixed nephritic and nephrotic
Nephritic syndrome
• Commonest cause– PIGN / PSGN or
post-infectious glomerulonephritis
Nephrotic syndrome
• Commonest cause– 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 Prerenal Renal
Na <20 >20
Urea >250 <150
U:P urea >20 <10
U:P Cr >20 <15
Sediment Nil ? 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
Fluid challenge 10-20 ml/kg normal saline over 1 hour, consider furosemide up to 5 mg/kg if no urine response
Overloaded 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
• Doctors
• Nurses
• Pharmacists
• Dietitians
• Play therapists
• Social worker
• Psychosocial team
Clinical problems
• How would you manage1. Hyperkalaemia2. Hyponatraemia3. Hypernatraemia4. Hypocalcaemia5. Hyperphosphataemia6. Acidosis7. Hypertension ?
Treatment - 1
• Hyperkalaemia– cardiac monitor; salbutamol; NaHCO3;– furosemide; Ca resonium and insulin:dextrose
• Hyponatraemia 2y to fluid overload– fluid restriction; RRT; hypertonic saline (Na<120)
• Hypernatraemia 2y to sodium retention– furosemide; dialysis (if oliguria)
• Hypocalcaemia is multifactorial– 1-alphahydroxycholecalciferol– calcium supplements
Treatment - 2
• Hyperphosphataemia– dietary phosphate restriction– phosphate binders
• Acidosis– 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 ?