Nephrology Division King Khalid University Tutorial Med Course 441 1

14 year old Saudi Male c/o fever-headache for 10 days General malaise Dark urine x 3 days 2

HPI Fever intermittent Muscular joint pain Urine character Edema No skin rash 3

PH & Med ◦ Antibiotic and NSAID Social Hx S. review FH 4

Examination BP : 160/90 mmHg and pulse rate: 120/min Temperature : 39 ºC Respiration: 25/min. pale Look Sick Puffiness in face Head and neck JVP 5

Chest Examination Normal percussion Normal TVF Normal breath sound Vesicular breathing S 1 increase S 2 N S 3 positive Pansystolic murmur ◦ Radiation to axilla ◦ Grade IIII 6

Abd ◦ Tend epigastic ◦ Tend loins ◦ BS +ve CNS ◦ Normal M.S. /Normal 7

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 9

Differential Diagnosis of Hematuria ARF-AKI-ATN ◦ Acute glomerulonephritis (post-infection) ◦ RPGN ◦ IgA ◦ Hemolytic uremic syndrome ◦ NSAID Hemolytic AnemiaIgA Nephropathy Hemolytic uremic 10

Investigation WBC 15,000 cells/microliter ◦ Hb – 100 g/L ◦ Plat – 150 g/L ◦ ESR 90 PT normal ◦ PPT normalSec ◦ BI normalSec 11

U&E Scr - 210µmol/L Urea – 20mmol/L K – 6mmol/L Na – 125 mmol/L Ca – 1.9 mmol/L Albumin – 28 g/L 12

Urine Analysis Many RBC Red cell cast abscent Protein – 1.2 g/24 hr 13

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U/S : kid size ENLARGE 12.2 cm 15

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Treatment Patient receive ceftriaxone IV and IV fluid TREAT HYPERKALEMIA 18

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Follow – up: S Cr – 300 µmmol/L JVP Oliguria Edema 20

Investigations for Glomerulonephritis Regular follow-up and U&E Antistreptolysin O (ASO) ANA, Anti-DNA C 3 -C 4 ANCA (p,c) HCV Antibody (HBsAg) HIV RF Cryoglobulin Anti-basement membrane anti-body (with lung hemorrhage 21

Management IV Lasix Repeat urine analysis ◦ RBC cast Kidney biopsy : RPGN Serology tesy : all negative RF: -negative Final diagnosis Anti-glomerular basement membrane anti- bodies 22

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) 23

Complications of acute glomerulonephritis Hypertension Pulmonary edema Hyperkalemia Encephalopathy convulsion Electrolyte disturbance Pericaditis Gastroentritis Peptic ulcer 24

Management of Glomerulonephritis Treat the cause Conservative management Dialysis 25

Acute post-infection glomerulonephritis Often associated with group A B-hemolytic streptococcal type 12 infection Also staphylococcus or viruses 26

Acute Glomerulonephritis Symptoms occur 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 C 3, normal C 4 ◦ 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 30

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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 32

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 GN Type 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) 34

Rapidly progressive GN Develops over a period of days and weeks Primarily adults in 50’s and 60’s Progresses to renal failure in a few weeks or months Hematuria is common, may see proteinuria, edema or hypertension 35

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 36

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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 age Pulmonary hemorrhage and renal failure TREATMENT Early treatment is essential Pulse steroid (10 mg/kg/day for 3 – 5 days) Cyclophosphamide Plasmapheresis 41

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 Polyangitis Necrotizing 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) 43

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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 46

Treatment Plasmapheresis Severe manifestations of pumonary hemorrhage on presentation Dialysis – dependent renal failure upon presentation Concurrent anti-GBM antibodies 47

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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) 51

Hemolytic AnemiaIgA Nephropathy hemolytic uremic 52

HPI Fever intermittent Muscular joint pain No skin rash Urine character edema 53

Rapidly progressive glomerulonephritis Immune Complex ◦ Anti-pathogen Antibody – Post Infectious GN ◦ IgA Nephropathy ◦ Anti-nuclear antibodies – SLE ◦ C 3 Nephritis – MPGN ◦ Cryoglobulin – HCV and HBsAg Anti-glomerular basement antibodies ◦ GMB antibodies Antineutrophil cytoplasmic antibodies (ANCA) ◦ Wegener's granulomatosis ◦ Microscopic polyangitis 54