PROTEINURIA AND THE NEPHROTIC SYNDROME Heavy proteinuria > 3.5 g/day/1.73 m2 highly or poorly selective

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Text of PROTEINURIA AND THE NEPHROTIC SYNDROME Heavy proteinuria > 3.5 g/day/1.73 m2 highly or poorly...


    Beata Mladosievičová

    Institute of Pathophysiology

    Medical Faculty, Bratislava

  • The kidneys play a major role

    in regulating

    fluids, electrolytes, acids and bases,


  • Imbalances occur as the kidneys

    • increase the ability to excrete proteins


    • decrease the ability to excrete (water,

    electrolytes, wastes and acid-base

    products) .

  • The daily excretion of protein into the urine of normal subjects rarely exceeds 150 mg... the small quantity of protein: High molecular weight glycoproteins from the distal tubular epithelium


    daily urinary excretion of

    protein>150 mg/ day

    Unrelated to renal disease


  • Pathological proteinuria

    1. Overflow of plasma proteins in excessive concentration – Ig light chains

    2. Increased glomerular permeability – abnormalities of GFB 1-40 g of protein/d

    3. Tubular damage < 2 g/d

    4. Disease of the lower urinary tract

  • Glomerular permeability to proteins:

     the nature of the glomerular filter – Endo, GBM, Epi

    (pores in layers,

    charge-selective filter,

    blood flow)

     the properties of the proteins (size, shape, charge)

  • Bacterial, viral Ag(Ab)

    components of complement

    attraction of the Leu

    lysosomal enzymes, free oxygen radicals

    filter damage

  • Increased glomerular permeability:

    congenital NS

    minimal change disease (most common in children)

    glomerulosclerosis (hypertension, diabetes mellitus)

    glomerulonephritis (membranous common in adults)

    IK deposits*

    postinfectious – bacterial endocarditis, hepatitis, TBC

    malignancy – Ca lung, breast, cervix. colon, kidney, ovary, leukaemias, lymphomas

    renal transplant rejection

  • Glomerulosclerosis


    Heavy proteinuria > 3.5 g/day/1.73 m2 highly or poorly selective increased glomerular permeability* decreased tubular reabsorbtion

    Hypoproteinaemia (esp.hypoalbuminaemia) Edema (increased ECF in the interstitium) decreased oncotic pressure, increased aldosterone and ADH, sodium and water retention

    Hyperlipidaemia increased hepatic synthesis of lipoproteins

    Lipiduria - oval fat bodies, granular casts

  • Oval fat bodies

  • Complications of NS

    • Infection – skin, lungs, peritoneum

    • Premature atherosclerosis

    • Impaired coagulation – increased circulating levels fibrinogen, factors V and VIII, decreased

    antithrombin III, haemoconcentration

    • Disorders in vitamins, hormones and elements

    bound to plasma proteins

  • Clinical presentation of the NS:


    •edema - ankles, periorbital region, anasarca, pleural effusion

    • may be hypertension

    • thrombotic complications (renal vein!)

    • frothy urine (proteinuria), nocturia

  • Laboratory findings:

    Urine: heavy proteinuria, protein ++ or greater in

    the urine for 2 consecutive days

    casts: granular, hyaline, epithelial

    Blood: hypoalbuminemia

    globulines, hormones adrenocortical or

    thyroid may be low

    lipemia (elevated cholesterol, Tg)

    anemia (loss of transferrin, poor

    production of erythropoetin)

    increased levels of fVIII, fibrinogen, Tr, Er

  • Hematuria

    Generally, hematuria is defined as the presence of 5 or more red blood cells (RBCs) per high- power field in 3 of 3 consecutive centrifuged specimens obtained at least 1 week apart.

    Hematuria can be either gross - visible(ie, overtly bloody, smoky, or tea-colored urine) or


  • Hematuria

    • Renal

    • Postrenal - cystitis, stone, tumor,


    • Other – drugs, infections

  • Hematuria – renal causes

     Renal GLOMERULAR

    -postinf. GN, RPGN,



    interstitial, Tu, accident, cystic,


  • PHARAOH Nephritic sy




    RBC casts

    Antistreptolysin O titres



  • Nephritic sy in adults

    Abdominal abscess

    Hepatitis B or C

    Infective endocarditis

    Membranoproliferative GN

    Rapidly progressive glomerulonephritis



    Viral diseases: measles, mononucleosis,


  • Case

    • 40 yrs old patient. 5 months ago both leg

    edema slowly progressive, phlebography

    without thrombosis, fatigue 3 months, no

    drugs, general practitioner found


    • History: alcohol abusus successfully treated

    3 yrs ago

    • Physical exam: leg edema, back edema, soft

    pitting edema

  • Causes of generalized edema?

    • Hypoproteinemia (low intake, enteropathies,

    liver damage, nephrotic sy)

    • Heart failure (RAA)

    • Electrolyte and water dysbalance (primary

    hyperaldosteronism, renal failure,...

    • Acute GN

    • Hypothyreosis

    • Drugs

  • Causes of localized edema?

    • Flebotrombosis

    • Leg ischemia

    • Trauma

    • Inflammation

    • Lymphedema

    • Allergy

  • Case II cont

    • Clinical signs and symptoms of heart

    failure, liver damage, myxedema and GIT

    damage are not present

    • Drugs potentially associated with edema,

    such as corticoids, calcium antagonist and

    others were not given

  • Which examinations are


    • complete blood count,

    • proteins,

    • electrolytes (Na, K, Cl, Ca),

    • creatinín, urea,

    • glycemia,

    • lipids,

    • markers of inflammation

  • Which next exams?

    • Liver test (AST,ALT, bilirubín...),

    • urine test,

    • X ray chest (pulmonary edema),

    • Sonography (ascites, kidneys, liver),

    • EKG

  • Results

    • ERY a Hb decreased,

    • FW a CRP mild increase,

    • Total proteins in blood and albumins


    • cholesterol and TG increased

    • liver test normal

    • creatinin, urea normal

    • EKG, X ray, abdominal and heart

    sonography normal

  • Conclusion

    • Low probability of heart, liver and

    kidney failure

  • Next exams?

    • Quantitative and qualitative exam of

    proteins during 24 hours, electrophoresis

    • Systemic disorders (ASLO, RF, antinuclear


    • Renal biopsy

  • Results

    • IgG low (excluded myeloma and systemic


    • ASLO,RF, antinuclear ff negat. excluded

    systemic disorders

    • Proteinuria 36g/day • Histology on biopsy: focal segmental


  • Therapy

    • Diuretics,

    • Corticoids

    • ACE inhibitors

  • Later after 6 months- worsening

    • Dialysis and planned transplantation

  • Hematuria could also be

    attributed to

    - non-nephrologic bleeding (e.g. menstruation), • But many are false positive findings due to the

    use of certain drugs or consumption of certain

    foods (e.g. mangold).

  • • Transient hematuria is common (40% in the

    general population)

    • Persistent hematuria (defined as urine

    positive in two out of three consecutive

    dipsticks, e.g. over a one to two weeks

    period) in just 2.5–4.3%