Mr. I.K 58 years old Hospitalized because of marked pitting peripheral edema (bilateral crural and perimalleolar edema) and uncontrolled blood pressure (BP 150/100 mmhg under treatment). since age 54 years old, arterial hypertension, treated with 2 antihypertensives, followed by progressive lower extremity edema. not allergic no occupational exposure to toxic environmental agents smokes, approximately 20 cigarettes per day drinks small amounts of alcohol no family history no blood transfusions obese: BMI 31 no leg varicosities
Diff. diagnosis of bilateral leg edema Drugs : Calcium channel blockers (especially Nifedipine, Amlodipine) Venous insufficiency Heart failure Pulmonary hypertension Nephrotic syndrome Liver disease Hypothyroidism Idiopathic edema
Laboratory tests Hb 13,2 g/dl, Hematocritis 38.6%, Leucocytes 8100, Platelets 330000 Creatininemia 1.1 mg/dl, uremia 42 mg/dl, uricemia 8.1 mg/dl (2-7.2), CRP 1.11 Proteinemia 5.3 (6.4-8.3), albuminemia 2.4 g/dl (3.2-5.5) Trigliceridemia 262, HDL Cholesterolemia 31, Total cholesterolemia 280 mg/dl, LDL Cholesterolemia 180 mg/dl, glicemia 82 mg/ml Bil.tot 1.07 mg/dl, AST 18 UI/l, ALT 1 UI/l, ALP 52 UI/l, GGT 16 UI/l, Sodium 139 mmol/l, potasium 4.2 mmol/l Urine dipstick: albumin ++++ hematuria ++ Urine microscopy: 3 red blood cells per high power field Proteinuria 24 hours 21 g Albuminuria 24 hours 5,2 g Uroculture negative Abdominal Ultrasound: normal Echocardiography: Left ventricular hypertrophy, Diastolic dysfunction, SIV 14 mm, EF 66%, Pulmonary artery pressure normal TSH 0.5 microui/ml (0.27-4.2), FT3 2.8 pg/ml (2.6-4.4), FT4 1.36 mg/dl (0.93-1.7)
Nephrotic Syndrome Criteria Proteinuria > 3.5 g/24 h Hypoalbuminemia <2.5 g/dl Edema Hyperlipidemia
Possible complications Hypertension Chronic renal disease c GFR 74.7 ml/min/1.73 m2 Chronic renal disease stage 2 with moderated decrease of GFR (GFR 60-89) Hypercoagulability and thromboembolism Antithrombine III 91% (80-120%) No antithrombin III deficiency Loss of vitamin D vitamin D 31 microg/l (30-80 microg/l), PTH 40 ng/l (10-65) Infections
Possible causes/associations of nephrotic syndrome Idiopathic glomerular disease : Focal segmental glomerulosclerosis and Membranous glomerular disease (the most two common primary causes), Minimal change glomerular disease, Membranoproliferative glomerular disease (for example, IgA) Diabetes mellitus (the most common secondary cause) Collagenosis: Lupus erythematosus, Scleroderma Vasculitis: Henoch Schoenlein nephritis Drug Abuse : Heroin, Interferon, Gold, Penicillamine, NSAID, Lithium Infections: HIV, HCV, HBV, Syphilis, Malaria, Tuberculosis, Epstein Barr virus Amyloidosis Malignancy : Carcinoma (bronchus,breast,colon, stomach, kidney), Multiple Myeloma, Lymphoma Hodgkin or non Hodgkin, Leukemia, Melanoma
(Diabetes Mellitus?) HBA1C 5.1% Serologic studies: ANA (serum antinuclear antibody) negative, anti DNA negative, C3 128 mg/dl (75-135), C4 24 mg/dl (20-58), (Hepatitis?) HBV positive, HBsAg 629 UI/ml, HBV DNA 945 UI/ml, HCV negative (Syphilis?) T.pallidum negative (HIV?) HIV Test negative (Amyloidosis?) Rectosigmoidoscopy with rectal biopsy: normal (Malignancy?)Thoracoabdominal CT: normal CEA, CA 19-9, PSA normal Serum protein electrophoresis: albuminemia 51% (56-68) α2 globuline 18.8% (6-11) α1 globuline 3.6 (2-4) β globuline 15 (8-14) γ globuline 11.6 (9-18) Imunoelectrophoresis: IgG 515 mg/dl (700-1600), Ig M 85 mg/dl (40-230), IgA 263 mg/dl ( 70-400) Bence Jones protein test negative
Renal biopsy Membranous glomerulonephropathy stage 1 associated with focal segmental glomerulosclerosis. Electron microscopy: *four glomeruli; in general thickened and irregular basement membranes due to subepithelial and intramembranous deposits *rare glomerular basement membrane spikes (new basement membrane material produced by epithelial cells) *small segmental sclerosis involving one glomerulus, *diffuse foot process effacement, *foam cells.
Diagnosis: MG stage 1 associated with FSGS. HBV inactive carrier Metabolic syndrome. Obesity. Arterial hypertension What would be the treatment? Prednisone and Ciclosporine induce remission Inactive carrier of hepatitis and low virus replication Prophylactic treatment with Lamivudine 100 mg, 1-0-0 Aspirin the risk of thromboembolic disease renal blood flow and glomerular filtration rate proteinuria Furosemid edema ACE inhibitors and angiotensin II receptor blockers systemic blood pressure and intraglomerular pressure proteinuria Allopurinol hyperuricemia Atorvastatin hyperlipidemia Intravenous albumin, prophylactic antibiotics, and prophylactic anticoagulation are not currently recommended
Is FSGS a predictor of renal outcome in patients with MG?* Some studies: Association MG-FSGS higher incidence and values of hypertension higher degree and longer duration of proteinuria higher serum creatinine microscopic haematuriaon urinanalysis significantly poorer prognosis than MG without FSGS Other studies: Have failed to demonstrate that segmental sclerosis could predict the progression to Renal disease *Chen Y, Cai G, Chen X (2013) Meta-Analysis of Association between Pathological Characteristics and Renal Outcomes in Adult Idiopathic Membranous Nephropathy. J Nephrol Therapeutic