glomerulonephritis an overview for the generalist - rcp london

GlomerulonephritisAn overview for the generalist

Dr Emma Vaux @VauxEmma

October 2019

What to do when blood & protein in urine?

What investigations should I do?

When do you refer ?

When do you

worry?

Chapter: Mechanisms of glomerular injuryoverviewAuthor(s): Neil TurnerFrom: Oxford Textbook of Clinical Nephrology

What treatments are you using?

Chapter: Mechanisms of glomerular injuryoverviewAuthor(s): Neil TurnerFrom: Oxford Textbook of Clinical NephrologyDownloaded from Oxford Medicine Online. © Oxford University Press

Case 1

• 50 year old

• Presents to ED

• 2 days D&V

• Clinically dehydrated

• BP 102/56

• Cr 154 mmol/l

• Urine dip 1+ blood

• Treated IV fluids

US KUB normal

Cr 66 mmol/l by day 2

What would you do next?

Q POLL OPEN

1 Discharge, no further follow up12.6%

2 Discharge, follow up with urologist3.15%

3 ‘Acute kidney screen’ & discharge18.9%

4 Discharge, GP follow up, repeat urine dip59.06%

5 Refer to nephrology6.3%

What would you do next?

A Discharge, no further follow up

B Discharge, follow up with urologist

C Acute kidney screen & discharge

D Discharge, GP follow up, repeat urine dip

E Refer to nephrology

Isolated non-visible haematuria

• ‘Trace' considered negative• 2 out of 3 dipsticks should be positive ≥ 1+ blood• Urine microscopy is rarely indicated • Proteinuria must be assessed

UrologyAge >45

NephrologyAge <45y

What do you do for isolated non-visible haematuria?

• Urology investigations appropriate for age

• Annual follow up with GP

– eGFR

– Urine ACR

– BP

Thin Basement membrane disease

When to refer with microscopic haematuria?

• Urine ACR > 30

• HT & age < 40yr

• FHx

• Progression CKD

Units eGFR = mL/min/1.73m2 ACR (albumin:creatinine ratio) = mg/mmol

Significant progression of CKD decline in eGFR of >5 within 1 year decline in eGFR >10 within five years

Urgent referral sustained decrease eGFR>25% within 12 monthsdecrease eGFR >15 within 12 months

IgA Nephropathy

• Commonest type of GN

• Frank haematuria following URTI,

isolated haematuria, proteinuria,

nephrotic syndrome, AKI, CKD

• Raised serum IgA ~50%

• Complement levels normal

• 20-40% eventually develop ESRD

• Can be secondary to liver disease

Normal

glomeruli

Mesangio

proliferative

GN

CrescenticGN

Global sclerosis

Treatment of IgAN

All patients Supportive treatment (ACEI/ARB

Mild disease Normal eGFR, proteinuria < 0.5g

Watch and wait

Moderate to severe disease urine protein>1g, eGFR >30 (KDIGO >50)

Corticosteroids for 6 months

Point of no returneGFR <30, severe chronic damage

Prepare for dialysis & transplantation

Crescentic IgA High dose steroid + cyclophosphamide

Alport Syndrome

When we would refer for genetic testing

• Family history

• Deafness

• Potential live kidney donor

Case 2

• Urgent referral by GP to AMU

• 34 yr female

• BP 176/92

• 2 days sore throat

• Urine dip 3+ blood 2+ protein

What is the most likely diagnosis?

Q POLL OPEN

1 Post streptococcal glomerulonephritis54.62%

2 Henoch Schönlein purpura25.21%

3 IgA nephropathy16.81%

4 Mesangiocapillary GN1.68%

5 SLE1.68%

What investigation would you do first?

Q POLL OPEN

1 ASOT titre24.8%

2 ANCA titre3.2%

3 Anti-GBM titre6.4%

4 ANA titre0.8%

5 Creatinine64.8%

What is the most likely diagnosis?

A Post streptococcal glomerulonephritis

B Henoch Schönlein purpura

C IgA nephropathy

D Mesangiocapillary GN

E SLE

What investigation would you do first?

A ASOT titre

B ANCA titre

C Anti-GBM titre

D ANA titre

E Creatinine

Henoch Schönlein Purpura

• IgA systemic vasculitis

• Purpuric rash, arthritis or arthralgia, & abdominal pain

• Most commonly seen in those <20 yr

• 10-30% ESRD at 15 yr

Differential diagnosis- hypersensitivity vasculitis- cryoglobulinemia,- SLE

TreatmentSupportiveSteroids – arthritis/abdo painKidney biopsy – active disease

Treatment of IgAN

All patients Supportive treatment (ACEI/ARB

Mild disease Normal eGFR, proteinuria < 0.5g

Watch and wait

Moderate to severe disease urine protein>1g, eGFR >30 (KDIGO >50)

Corticosteroids for 6 months

Point of no returneGFR <30, severe chronic damage

Prepare for dialysis & transplantation

Crescentic IgA High dose steroid + cyclophosphamide

Poststreptococcal GN

• Children & >60 yr

• Group A or C streptococci

• Acute nephritic syndrome

• Skin infection (several weeks) > throat infection (2 weeks)

• Raised ASOT, low C3

• Supportive treatment

• Unusual to need dialysis

Mesangioproliferative GN

• Young adults• ICX + complement mediated• Hypocomplementaemia, C3NF• HT

• Approximately 40% of patients progress to ESRD within 10 years of diagnosis

• Immune complex–mediated– Infections– Autoimmune diseases eg SLE– Monoclonal gammopathy (MGRS)

• Complement-mediated– Dense Deposit Disease– C3GN

• MPGN without immunoglobulin or complement deposition

– TTP/HUS– Antiphospholipid syndrome– Allograft nephropathy– Radiation nephritis– Malignant hypertension/sclerodema

Investigations blood & protein

• ANA, ANCA, anti-GBM, Rheumatoid Factor• Complement (low C3- post-infectious GN, MCGN,

SLE)• Immunoglobulins• CRP• ASOT• Infection…think IE, hepatitis C (& HIV)• (Cryoglobulins (HepC))

• Kidney biopsy

Case 3

• 68yr man• Respiratory clinic with obstructive sleep apnoea• c/o Swollen ankles

• No other PMHx; No other medication• Cr 96 mmol/l• BP 119/64• Urine dip 3+ protein• Urine ACR 340 mg/mol

What test would you do next?

Q POLL OPEN

1 US KUB16.67%

2 Kidney biopsy9.65%

3 Serum albumin60.53%

4 Echocardiogram5.26%

5 CXR7.89%

What test would you do next?

A US KUB

B Kidney biopsy

C Serum albumin

D Echocardiogram

E CXR

What would you not do next?

Q POLL OPEN

1 Start steroids64.42%

2 Refer nephrology0.96%

3 US KUB3.85%

4 Start diuretic therapy26.92%

5 Start VTE prophylaxis3.85%

What would you not do next?

• Start steroids

• Refer nephrology

• US KUB

• Start diuretic therapy

• Start VTE prophylaxis

What is the most likely diagnosis?

Q POLL OPEN

1 Minimal change GN20%

2 Diabetic nephropathy12.31%

3 Focal segmental glomerulosclerosis21.54%

4 Membranous GN43.08%

5 Hypertensive GN3.08%

What is the most likely diagnosis?

• Minimal change GN

• Diabetic nephropathy

• Focal segmental glomerulosclerosis

• Membranous GN

• Hypertensive GN

Membranous Nephropathy

Male; >40yr Young women ?SLE

Primary (associated with positive PLA2R)

Secondary (Hepatitis, SLE, drugs, tumours)

Patients with MN should have age-appropriate cancer screening

10-30% will develop ESRD within 10 years

Kidney International 2019 95, 268-280DOI: (10.1016/j.kint.2018.10.018)

Figure 3

Kidney International 2019 95, 268-280DOI: (10.1016/j.kint.2018.10.018)

Minimal Change Disease

• Commonest cause of NS in

children

• Primary vs Secondary

(Lymphoma, NSAID, Allergy)

• Response to corticosteroids

• Relapse 50-75%

Focal segmental glomerulosclerosis

• Histologic lesion• Primary – diagnosis of exclusion• Secondary – obesity, drugs,

infection• Familial• Variants eg collapsing –HIVAN

• High dose steroids• Renal survival

– Responders vs non-responders/untreated 80% vs <50% at 10 years

Risk of VTE: Increase with albumin < 28

Kidney International (2012) 81, 190

Case 4

52 yr man

Type I DM (aged 13yr), previous MI, heavy smoker

Increasingly SOBOE & ankle swelling

Diagnosed by GP with heart failure

Cr risen from 86mmol/l to 196 on diuretics

GP & community heart failure team worried about his management

What set of investigations would you do next?

Q POLL OPEN

1 U+Es, CXR, ECG, ECHO1.3%

2 U+Es, CXR, albumin, ECHO3.9%

3 U+Es, CXR, Urine ACR11.69%

4 U+Es, albumin, urine ACR, ECHO63.64%

5 U+Es, albumin, US KUB, ECHO19.48%

What set of investigations would you do next?

A U+Es, CXR, ECG, ECHO

B U+Es, CXR, albumin, ECHO

C U+Es, CXR, Urine ACR

D U+Es, albumin, urine ACR, ECHO

E U+Es, albumin, US KUB, ECHO

Case 4

52 yr man

Type I DM (aged 13yr), previous MI, heavy smoker

Increasingly SOBOE & ankle swelling

Diagnosed by GP with heart failure

Cr risen from 86mmol/l to 196 on diuretics

GP & community heart failure team worried about his management

Urine dip 3+ protein; ACR 290; albumin 29

Bp 189/92

What is the most likely cause of the nephrotic syndrome?

Q POLL OPEN

1 Heart failure1.06%

2 Diabetic nephropathy58.51%

3 Hypertensive nephropathy26.6%

4 Membranous Glomerulonephritis13.83%

What is the most likely cause of the nephrotic syndrome?

A Heart failure

B Diabetic nephropathy

C Hypertensive nephropathy

D Membranous Glomerulonephritis

50 yr man admitted the previous day with 2 day history severe arthralgias, fever, weight loss, epistaxis, and large painful purpuric lesions on his legs

• Creatinine 275 mmol/l not improving with intravenous fluid

• FBC: Hb 115; Plt 165• Urine dip 2+ blood 1+ protein• You learn that he has a history of cocaine abuse• Some of the acute screen is back – low C3 + C4

Case 5

Which ONE of the following is MOST likely to be found on renal biopsy?

POLL OPEN

1. Crescentic IgAN8.11%

2. Collapsing FSGS8.11%

3. Pauci-immune necrotising & crescentic GN37.84%

4. Thrombotic microangiopathy45.95%

A. Crescentic IgANB. Collapsing FSGSC. Pauci-immune necrotising & crescentic GND. Thrombotic microangiopathy

Which ONE of the following is MOST likely to be found on renal biopsy?

Chapter: Mechanisms of glomerular injuryoverviewAuthor(s): Neil TurnerFrom: Oxford Textbook of Clinical NephrologyDownloaded from Oxford Medicine Online. © Oxford University Press

It’s all about the protein….

Microscopic haematuria – age, urology, ACR >30, HT, FHx

Proteinuria - ACR >70; nephrotic

AKI +/- Progressive kidney disease

BP

Dear Dr

Please see this 33 year old lady whom I think might have nephrotic syndrome.

She has normal kidney function but her serum albumin is only 30.

Her liver function is normal.

Best wishes

Who to refer?Microscopic haematuria >40yr to urology

Significant proteinuria - ACR >30 with haematuria- ACR >70 (unless DM)- NephroticSignificant progression CKDPoor BP controlNon-resolving AKISystemic symptoms

TreatmentsStop thingsSupportive

Steroids

Calcineurin inhibitorsCyclophosphamideRituximabPlasma exchange

Renal replacement therapy