Nephrology DivisionKing Khalid University

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Prof. Jamal Alwakeel

Acute Glomeruloneph

ritisTUTORIAL MED COURSE 441

14 year old Saudi Male

c/o fever-headache for 10 days

General malaise

Dark urine x 3 days

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HPI

Fever intermittentMuscular joint

painUrine character Edema No skin rash

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PH & Med◦Antibiotic and NSAID

Social HxS. reviewFH

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Examination BP : 160/90 mmHg and Pulse rate: 120/min Temperature : 39 ºC Respiration: 25/min,

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Look Sick Pale Puffiness in face Head and neck JVP

Chest Examination

Normal percussionNormal TVFNormal breath soundVesicular breathingS1 increase

S2 N

S3 positive

Pansystolic murmurRadiation to axilla

◦ Grade III

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Abd◦ Tend epigastic◦ Tend loins◦ BS +ve

CNS◦ Normal

M.S. /Normal

Burbic rash in the leg 7

Initial Diagnosis

Fever? Infection vs autoimmune Disease

Murmur; M R vs VSD

HEAMATURIA

Urine Sample with hematuria 8

In it ia

l Diagnosis

HematuriaSystemic

◦ Hemolytic Anemia◦ Embolization ◦ Anti-coagulant

Surgical◦ Stone ◦ Tumor◦ Papillary◦ APKD

Medical◦ Acute kidney injury◦ Glomerulonephritis◦ Rapid progressive glomerulonephritis

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Differential Diagnosis of Hematuria ARF-AKI-ATN

◦ Acute glomerulonephritis (post-infection)◦ RPGN◦ IgA◦ Hemolytic uremic syndrome◦ NSAID

Hemolytic Anemia IgA Nephropathy Hemolytic uremic 10

Investigation

WBC 15,000 cells/microliter◦ Hb – 100 g/L◦ Plat – 150 g/L◦ ESR 90

PT normal◦ PPT normal Sec◦ BI normal Sec

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U&E S.cr - 210µmol/LUrea – 20mmol/LK – 6mmol/LNa – 125 mmol/LCa – 1.9 mmol/LAlbumin – 28 g/L

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Urine Analysis

Many RBCRed cell cast absentProtein – 1.2 g/24 hr

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U/S : kid size ENLARGE 12.2 cm

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Treatment

Patient receive ceftriaxone IV and IV fluid

TREAT HYPERKALEMIA

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Follow – up:

S Cr – 300 µmmol/LJVPOliguriaEdema

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Investigations for Glomerulonephritis

Regular follow-up and U&EAntistreptolysin O (ASO)ANA, Anti-DNAC3-C4

ANCA (p,c)HCV Antibody (HBsAg)HIVRFCryoglobulinAnti-basement membrane anti-body (with

lung hemorrhage

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Management IV LasixRepeat urine analysis

◦RBC castKidney biopsy : RPGN-infectionSerology test : C3 lowRF: -negativeFinal diagnosis: Infection glomerulonephritis-

RPGNAnti-glomerular basement membrane anti-

bodies

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Glomerular Disease – Acute Glomerulonephritis

Post infectious glomerulonephritis

Group A Strep Infection Infective endcarditis

Membranoproliferative glomerulonephritis:

Systemic lupus erythematosus

Hepatitis C virus

IgA Nephropathy (Buerger’s Disease)

Rapidly progressive glomerulonephritis

Type I RPGN (direct antibody)

Good Posture syndrome

Type II RPGN (immune complex)

Post infectious Systematic lupus

erythematosus Henoch – Schonlein pupura

(IgA)

Type III RPGN (pauci-immune)

Vasculitis (Wegener granulomatosis; poiyarteritis nodosa-microscopic polyangitis)

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Complications of acute glomerulonephritis

HypertensionPulmonary edemaHyperkalemiaEncephalopathy convulsionElectrolyte disturbancePericaditisGastroentritisPeptic ulcer

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Management of Glomerulonephritis

Treat the causeConservative

managementDialysis

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Acute post-infection glomerulonephritis

Often associated with group AB-hemolytic streptococcal type 12

infectionAlso staphylococcus or viruses

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Acute Glomerulonephritis

Symptoms occur 10-21 days after infection◦ Hematuria◦ Proteinuria (<1gm/24 hr)◦ Decreased GFR, oliguria◦ Hypertension◦ Edema around eyes, feet and ankles◦ Ascites or pleural effusion

Antistreptolysin O (ASO), Low C3, normal C4

◦ Kidney biopsy immune complexes and proliferation 27

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Proliferative GN-post streptococcal

This glomerulus is hypercellular and capillary loops are poorly defined This is a type of proloferative glomerulonephritis known as post-streptococcal

glomerulonephritis 29

Post-streptococcal GN

Post-streptococcal glomerulonephritis is immunologically mediated, and the immune deposits are distributed in the capillary loops in a

granular, bumpy pattern because of the focal nature of the deposition process

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Post-streptococcal glomerunephritis

Conservative Treatment (acute kidney injury

Improves 1 – 4 weeks, C3 normalizes in 1 – 3 months, hypertension improves 1 – 3 months, intermittent hematuria x 3 years

99% complete recovery in children and 85% in adult

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IgA nephropathy (Buerger’s Disease)

Most common acute glomerulonephritis in US, South East Asia

Associated with H.S. Purpura Upper respiratory (50%) in 1 – 2

days (synpharyngitic hematuria) Primary versus secondary (IBD,

Liver disease, SLE, vasculitis) 50% risk of CRF Proteinuria, hypertension, renal

insufficiency predict worse prognosis

50% increase IgA, normal compliments

TREATMENT OF CONSERVATIVE ACEi

HIGH RISK: patient prednisone and alkylating agent

Cyclophosphamide-azothroprim & ASA & ACEi & tosilectomy 33

Rapid Progressive GNType I RPGN (direct antibody)

◦ Good pasture syndrome

Type II RPGN(immune complex)◦ Post infectious◦ Systematic lupus erythematosus◦ Henoch-schonlein purpura (IgA)◦ Cryoglobulinemia

Type II (pauci-immune)◦ Vasculitis (Wegener granulomatosis,

microscopic polyangitis, poplyarteries nodosa)

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Rapidly progressive GN

Develops over a period of days and weeks

Primarily adults in 50’s and 60’sProgresses to renal failure in a few

weeks or monthsHematuria is common, may see

proteinuria, edema or hypertension

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Rapidly progressive (Crescentic) Glomerulonephritis

Morphology◦ Crescent formation

◦ Crescents are formed by proliferation of parietal cells

◦ Infiltrates of WBC’s & fibrin deposition in Bowman’s space

◦ EM reveals focal ruptures in the GBM

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Goodpasture Syndrome

Antibody formation against pulmonary and glomerular capillary basement membranes

Damage glomerular basement membraneMen – 20 to 30 years of agePulmonary hemorrhage and renal failure

TREATMENT Early treatment is essential Pulse steroid (10 mg/kg/day for 3 – 5 days)CyclophosphamidePlasmapheresis

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Goodpasture’s syndrome

This immunoflourescence micrograph shows positivity with antibody to IgG has a smooth, diffuse, linear pattern that is characteristic for glomerular basement antibody with Goodpasture’s syndrome 42

Microscopic PolyangitisNecrotizing vasculitis of small – and medium –

sized vessels in both the arterial and venous circulations

Frequently involves the lung and the kidney with typical complications of hemorrhage and glomerulonephritis

Usually positive p-ANCA (anti-myeloperoxidase)

Usually positive c-ANCA (ant-proteinase 3)

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Treatment Initial TherapyCombination cyclophosphamide-corticosteroid

therapy

Pulse methyl prednisone (10 mg/kg/day for 3-5 days)

A slow steroid taper, with the goal of reaching 20 mg of prednisone per day by the end of two months and an overall glucocorticoid course of between 6 and 9 months

Either daily oral or monthly intravenous cyclophosphamide 45

Treatment

Plasmapheresis

Severe manifestations of pulmonary hemorrhage on presentation

Dialysis – dependent renal failure upon presentation

Concurrent anti-GBM antibodies

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