Nephrology Division King Khalid University Acute Glomerulonephritis Tutorial Med Course 441 Prof. Jamal Alwakeel Nephrology Division King Khalid University

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

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

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

Examination BP : 160/90 mmHg and Look Sick Pale Puffiness in face Pulse rate: 120/min Temperature : 39 ºC Respiration: 25/min, Look Sick Pale Puffiness in face Head and neck JVP

Chest Examination Normal percussion Normal TVF Normal breath sound Vesicular breathing S1 increase S2 N S3 positive Pansystolic murmur Radiation to axilla Grade III

Abd CNS M.S. /Normal Burbic rash in the leg Tend epigastic Tend loins BS +ve CNS Normal M.S. /Normal Burbic rash in the leg

Urine Sample with hematuria Initial Diagnosis Fever? Infection vs autoimmune Disease Murmur; M R vs VSD HEAMATURIA Urine Sample with hematuria

Initial Diagnosis Systemic Surgical Medical Hematuria Hemolytic Anemia Embolization Anti-coagulant Surgical Stone Tumor Papillary APKD Medical Acute kidney injury Glomerulonephritis Rapid progressive glomerulonephritis Initial Diagnosis

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

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

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

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

U/S : kid size ENLARGE 12.2 cm

Patient receive ceftriaxone IV and IV fluid Treatment Patient receive ceftriaxone IV and IV fluid TREAT HYPERKALEMIA

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

Investigations for Glomerulonephritis Regular follow-up and U&E Antistreptolysin O (ASO) ANA, Anti-DNA C3-C4 ANCA (p,c) HCV Antibody (HBsAg) HIV RF Cryoglobulin Anti-basement membrane anti-body (with lung hemorrhage

Management IV Lasix Repeat urine analysis RBC cast Kidney biopsy : RPGN-infection Serology test : C3 low RF: -negative Final diagnosis: Infection glomerulonephritis- RPGN Anti-glomerular basement membrane anti-bodies

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)

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

Management of Glomerulonephritis Treat the cause Conservative management Dialysis

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

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

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

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

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

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

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)

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

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

Goodpasture Syndrome TREATMENT Early treatment is essential 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

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

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)

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

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

Thank you…