Nephrology Division King Khalid University Tutorial Med Course 441 Tutorial Case

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 pulse rate 120/min ◦ Temp : 39 ºC Resp 25/min. pale Look Sick Puffiness in face Head and neck JVP

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

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

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

Initial Diagnosis Hematuria Systemic ◦ Hemolytic Anemia ◦ Embolization ◦ Anti-coagulant Surgical ◦ Stone ◦ Tumor ◦ Papillary ◦ APKD Medical ◦ Acute kidney injury ◦ Glomerulonephritis ◦ Rapid pogressive glomerulonephrtis ◦ IgA Nephropathy

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

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

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

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

U/S : kid size ENLARGE 12.2 cm

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 C 3 -C 4 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 Serology tesy : all negative RF: -negative Final diagnosis 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 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

Proliferative GN-poststretococcal 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 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 pumonary hemorrhage on presentation Dialysis – dependent renal failure unpon presentation Concurrent anti-GBM antibodies