GLOMERULOPATHIES

Hasyim kasim MD

Glomerulopathies
Glomerulopathy : a group of diverse conditions including, but not limited to, glomerulonephritis having in common the fact that the disease process begins in the glomerulus or that the glomerulus is the most importantly diseased part of the nephron. Glomerulopathies are the most common causes of end-stage renal disease

Clinical presentation of glomerular disease

I. Acute glomerulonephritis

II.

Rapidly progressive glomerulonephritis

III. Chronic glomerulonephritis IV. Persistent urinary abnormalities with few or no symptoms V. Nephrotic syndrome

Acute glomerulonephritis
Oligouria Hematuria : red blood casts

Proteinuria : usually < 3 g/day

Edema Hypertension

Abrupt onset, usually self-limiting

Rapidly progressive glomerulonephritis

Renal failure over days/weeks
Proteinuria : usually < 3 g/day Hematuria : red blood casts

Blood pressure often normal

May have other features of vasculitis

Chronic glomerulonephritis
Hypertension
Renal insuficiency Proteinuria > 3g/day

Shrunken smooth kidneys

Persisting urinary abnormalities with few or no symptoms

Reccurent or persistent hematuria with or without

abnormal proteinuria Isolated non-nephrotic glomerular proteinuria

( asymptomatic proteinuria without hematuria ;

isolated proteinuria )

Nephrotic syndrome
Clinical entity having multiple causes and characterized by increased glomerular permeability manifested

by massive proteinuria and lipiduria.

Massive proteinuria > 3.5 g/day/1.73m2 body surface area in the absence of a depressed GFR.

Clinical Features of The Nephrotic Syndrome

Manifestations of the nephrotic syndrome itself Signs and symptoms determined by the underlying disease involving the kidney

Differentiation between nephrotic and nephritic syndrome

Typical features Nephrotic Nephritic

Onset
Edema Blood pressure Jugular venous pressure Proteinuria Hematuria Red-cell casts Serum albumin

Insidious
++++ Normal Normal/low ++++ May/may not occur Absent low

Abrupt
++ Raised Raised ++ +++ Present Normal/slightly reduce

Clinical manifestation of nephrotic syndrome : Oedema

Hypertension
Dyslipidemia Hypercoagulable state

Hypoproteinemia / proteinuria
Progressive renal failure Trace metal deficiencies Endocrine disturbances Infectious / immunodeficiency states

Classification of the disease states associated with the development of nephrotic syndrome I. Idiopathic nephrotic syndrome due to Primary Glomerular Disease

II.Nephrotic syndrome associated with spesific etiologic events or in which glomerular disease arises as a complication of other disease
1. 2. 3. 4. 5. 6. 7. Medications Allergens, venoms, immuization Infection ( bacterial, viral, protozoal, helminthic ) Neoplasmic ( solid tumors, leukemia and lymphoma ) Multisystem disease Heredofamilial and metabolic disease Miscellaneous

Formation of nephrotic edema Underfill

Proteinuria Hypoalbuminemia Plasma colloid Oncotic pressure
Starling forces

Overfill
Primary tubular defect causing sodium retention

Normal/raised plasma volume Vasopressin normal RAS activated Aldosterone

Reduced plasma volume Vasopressin ANP normal/low

Aldosterone
ANP

Water retention Sodium retention

Edema

Management of oedema in nephrotic syndrome

Mild Dietary NaCl restriction ( to 3-4 g NaCl per day ) Support stockings Hydrochlorothiazide 12.5-50 mg/day ( if GFR > 50 ml/min ) Frusemide 40-80 mg/day ( if GFR < 70 ml/min ) Moderate Continue NaCl restriction ( Frusemide 160-480 mg/day or bumetamide 1-2 mg/day or torsemide 40-160 mg/day ) Severe Continue NaCl restriction Oral or IV frusemide 160-480 mg/day ( or bumetanide or torsemide ) plus metalozone 2.5-10 mg/day Refractory Continuous IV infussion or frusemide ( 20 mg/h ) or bumetanide ( 1 mg/h ) after a loading dose

or or

Hyperosmotic salt-poor albumin ( 25-50 g ) mixed with 120 mg of furosemide Slow continuous veno-venous ultrafiltration using a highly permeable membrane

Plasma lipid concentrations in nephrotic syndrome

Increased Very low density lipoproteins Intermediate density lipoproteins Low density lipoproteins Apolipoprotein B Apolipoprotein CIII High density lipoproteins Lipoprotein (a) Total cholesterol Triglycerides ( when serum albumin < 2 g/dl) Unchanged Apolipoprotein AI Apolipoprotein AII Apolipoprotein CIII Decreased High density lipoprotein 2

Therapy of dyslipidemia in nephrotic syndrome

Only full successful when the underlying cause is remidied and long term complete remission of proteinuria are induced Reduced cholesterol and saturated fat intake ( relatively ineffective ) Drugs : HMG co-enzyme A reductase inhibitors ( lovastatin, simvastatin, fluvastatin, atorvastatin )

Coagulation abnormalities in nephrotic syndrome Increased ( prothrombotic ) Fibrinogen Platelets ( and platelet adhesiveness ) Plasma viscosity ( cholesterol, lipid ) Lipoprotein (a) Plasminogen activator inhibitor Decreased ( antithrombotic ) Active protein C Active protein S Antithrombin III

Prothrombotic state are correlated with serum albumin levels Serum albumin < 2-2.5 g/dl appears to be associated with an increased risk of thromboembolism

Diagnostic approach in nephrotic syndrome

I. Clinical

II. Laboratory studies

III. Renal biopsy

I. Clincial
History Preexisting disease Previous infection Drug ingestion Arthritis, rash Current pregnancy Family history of renal disease Physical examination Severe obesity Rash, arthritis Diabetic retinopathy Hypertension Evidence of malignancy Lipodystrophy Lymphoadenopathy/hepatosplenomegaly

II. Laboratory Studies

Urinalysis In all cases ( non-diagnostic ) Creatinine clearance Serum protein electrophoresis Serum total cholesterol, lipoprotein Serum ionized calcium Parathyroid hormone

In selected cases ( to established the diagnosis ) Complement level Antinuclear antibody assay Cryoglobulins Hepatitis and HIV serology Serum and urine immunoelectrophoresis

III. Renal biopsy

Minimal change disease

Focal segmental glomerulosclerosis Membranous nephropathy Membranoproliferative glomerulonephritis Other glomerulonephritis

Suggested approach for initial treatment ( Minimal change disease )

Children
Prednisone 60 mg/m2/day until remission, then 40 mg/m2/48 h for 12 weeks, then reduce by 5-10 mg/m2/48 h every month.

Adults
Prednisone 1mg/kg/day until remission or for 6 weeks, then 1.6 mg/kg/48 h for 1 month, then reduce by 0.2-0.4 mg/kg/48 h.

Elderly
Prednisone 1 mg/kg/day until remission or for 4 weeks, then 0.8 mg/kg/day for 2 weeks, then 1.6 mg/kg/48 h for 2 weeks. Then reduce by 0.4 mg/kg/48 h every 2 weeks. If no remission continue with 1.2 mg/kg/48 h for another 4 weeks then reduce.

Contraindications to prednisone
Cyclophosphamide 2 mg/kg/day or chlorambucil 0.15mg/kg/day for 8-12 weeks

Definitions used to describe responses and relapses in patients with minimal Change nephropathy
Complete remission Proteinuria lower than 4 mg/m2/day in children or lower than 0.2 g/day in adults for three consecutive days Proteinuria between 4 and 40 mg/m2/dayin children or between 0.21 and 3.5 g/day in adults for three consecutive days Proteinuria excreeding 4 mg/m2/day in children or 0.2 g/day in adults for at least 1 week, in patients who were in complete remission Proteinuria exceeding 40 mg/m2/day in children or 3.5 g/day in adults for at least 1 week, in patients who were in complete or partial remmision Patients with 2 or more episodes of the nephrotic syndrome in 6 months or 3 or more episodes of the nephrotic syndrome in 12 month Reappearance of the nephrotic syndrome within 2 weeks after reduction or discontinuation of glucocorticoids Controversial

Partial remission

Relapse of proteinuria

Relapse of nephrotic syndrome Frequent relapses

Steroid-dependent nephrotic syndrome Steroid-resistant nephrotic syndrome

TERIMA

KASIH