Nephrology DivisionKing Khalid University

Tutorial Med Course 441

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14 year old Saudi Malec/o fever-headache for 10 daysGeneral malaiseDark urine x 3 days

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HPIFever

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/minTemperature : 39 ºC Respiration: 25/min. paleLook SickPuffiness in faceHead and neckJVP

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Chest ExaminationNormal percussionNormal TVFNormal breath soundVesicular breathingS1 increaseS2 NS3 positivePansystolic murmur

◦Radiation to axilla◦Grade IIII 6

Abd◦Tend epigastic◦Tend loins◦BS +ve

CNS◦Normal

M.S. /Normal

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Initial Diagnosis

Fever? Infection vs autoimmune Disease

Murmur ; M R vs VSD

HEAMATURIA

Urine Sample with hematuria 8

Initial Diagnosis

Hematuria Systemic

◦ Hemolytic Anemia◦ Embolization ◦ Anti-coagulant

Surgical◦ Stone ◦ Tumor◦ Papillary◦ APKD

Medical◦ Acute kidney injury◦ Glomerulonephritis◦ Rapid pogressive glomerulonephrtis◦ IgA Nephropathy

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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

InvestigationWBC 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 Scr - 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

abscentProtein – 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 fluidTREAT 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-C4ANCA (p,c)HCV Antibody (HBsAg)HIVRFCryoglobulinAnti-basement membrane anti-body

(with lung hemorrhage 21

Management IV LasixRepeat urine analysis

◦RBC castKidney biopsy : RPGNSerology tesy : all negativeRF: -negativeFinal diagnosisAnti-glomerular basement

membrane anti-bodies22

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 syndromeType 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) GlomerulonephritisMorphology

◦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 membrane

Men – 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 Therapy

Combination 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

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Treatment PlasmapheresisSevere manifestations of pumonary

hemorrhage on presentationDialysis – dependent renal failure

upon presentationConcurrent anti-GBM antibodies

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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 (cryoglobulinemia,

Wegener granulomatosis; popular arteritis nodosa)

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Hemolytic Anemia IgA Nephropathy hemolytic uremic 52

HPIFever

intermittentMuscular joint

pain No skin rashUrine character edema

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Rapidly progressive glomerulonephritis

Immune Complex◦ Anti-pathogen Antibody – Post Infectious GN◦ IgA Nephropathy◦ Anti-nuclear antibodies – SLE◦ C3 Nephritis – MPGN ◦ Cryoglobulin – HCV and HBsAg

Anti-glomerular  basement antibodies◦ GMB antibodies

Antineutrophil cytoplasmic antibodies (ANCA)◦ Wegener's granulomatosis◦ Microscopic polyangitis

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