PROTEINURIA, NEPHROTIC AND NEPHRITIC SYNDROME

Beata Mladosievičová

Institute of Pathophysiology

Medical Faculty, Bratislava

The kidneys play a major role

in regulating

fluids, electrolytes, acids and bases,

osmolality

Imbalances occur as the kidneys

• increase the ability to excrete proteins

or

• 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

PROTEINURIA

daily urinary excretion of

protein>150 mg/ day

Unrelated to renal disease

Pathological

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

THE NEPHROTIC SYNDROME

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:

•anorexia

•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

microscopic.

Hematuria

• Renal

• Postrenal - cystitis, stone, tumor,

accident

• Other – drugs, infections

Hematuria – renal causes

Renal GLOMERULAR

-postinf. GN, RPGN,

glomerulosclerosis...

Renal NONGLOMERULAR–

interstitial, Tu, accident, cystic,

hydronephrosis...

PHARAOH Nephritic sy

Proteinuria

Hematuria

Azotemia

RBC casts

Antistreptolysin O titres

Oliguria

Hypertension

Nephritic sy in adults

Abdominal abscess

Hepatitis B or C

Infective endocarditis

Membranoproliferative GN

Rapidly progressive glomerulonephritis

SLE

Vasculitis

Viral diseases: measles, mononucleosis,

mumps

Case

• 40 yrs old patient. 5 months ago both leg

edema slowly progressive, phlebography

without thrombosis, fatigue 3 months, no

drugs, general practitioner found

hypoproteinemia

• 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

suggested?

• 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

decreased

• 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

faktors)

• Renal biopsy

Results

• IgG low (excluded myeloma and systemic

diseases),

• ASLO,RF, antinuclear ff negat. excluded

systemic disorders

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

glomerulosclerosis

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%