Post-infectious glomerulonephritis Stephen Marks Consultant Paediatric Nephrologist Great Ormond Street Hospital for Children and UCL Institute of Child

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)





Question (a)





Question (b)


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)


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)



Question (c)



Question (d)



Question (d)



Question (e)




Question (e)




Question (f)







Question (f)







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


Nephritic syndrome

• Haematuria

• Proteinuria

• Oliguria

• Hypertension

Nephrotic syndrome


Nephritic syndrome

• Haematuria

• Proteinuria

• Oliguria

• Hypertension

Nephrotic syndrome

• Proteinuria– > 40mg/m2/hour– > 1g/m2/day

• Hypoalbuminaemia– < 25g/l

• Oedema• (Hyperlipidaemia)


Nephritic syndrome

• Commonest cause– PIGN / PSGN or

post-infectious glomerulonephritis

Nephrotic syndrome

• Commonest cause– MCD / MCNS or

minimal change nephrotic syndrome


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 ?

Documents

Post-infectious glomerulonephritis Stephen Marks Consultant Paediatric Nephrologist Great Ormond Street Hospital for Children and UCL Institute of Child