Proteinuria

Proteinuria
• Urinary excretion of protein more than normal.
• <150 mg/day
• Most predominant protein in urine is albumin
Albuminuria:
• Urinary excretion of Albumin more than normal
• <30 mg/day or <20µg/min
Source of protein in urine:
• Plasma (by filtration of plasma): albumin,
prealbumin, beta2 macroglobulin, ceruloplasmin,
haptoglobin
• Renal tubule (by secretion/ desquamation of
tubular cells): Tamm-Horsfall protein, low MW
globin
• Loss of glomerular/ tubular integrity causes
abnormal urinary secretion of protein
AER:
<30 mg/day or <20 µg/min
PER:
<150 mg/day
• Practically AER & PER are identical but in tubular
& overflow proteinuria PER is more than AER
Types of albuminuria: (quantitative)
1. Microalbuminuria:
• urinary AER 30-300 mg/day
• increased urinary albumin excretion
• but urinary dipstick test is negative
2. Macroalbuminuria:
• urinary AER >300 mg/day
• increased urinary albumin excretion
• but urinary dipstick test is positive
Types of proteinuria: quantitative
1. microproteinuria: urinary PER 150-500mg/day
2. Macroproteinuria: urinary PER >500 mg/day
Pathophysiological types of proteinuria:
1. Benign proteinuria
2. Glomerular proteinuria
3. Tubular proteinuria
4. Overflow proteinuria
5. Functional proteinuria
Benign proteinuria:
• PER <1 g/day
• Transient
• Occurs in physical activity, trauma, stress, fever
Glomerular proteinuria:
• PER >2g/day
• Albumin predominance
• Due to loss of glomerular integrity & increased
glomerular capillary permeability
• Glomerulonephritis, NS
Tubular proteinuria:
• PER <2 g/day
• Globin dominant
• Due to secondary loss of tubular integrity &
decreased reabsorption of protein
• Pyelonephritis, ATN
Overflow proteinuria:
• Due to increased production of low MW protein
& increased serum protein concentration
• Protein filtration> protein reabsorption
• Bence jones proteinuria in multiple myeloma
Functional proteinuria: (non renal cause)
Acute infection & septicemia
Leukemia
Preeclampsia
Hyperthyroidism
Cardiac disease
Clinical types of proteinuria:
1. asymptomatic: PER< 1g/day
2. Moderate proteinuria: PER 1-3 g/day
3. Massive proteinuria: PER > 3 g/day
Causes of proteinuria/ albuminuria:
Renal disease:
• GN, pyelonephritis
• NS, ATN
• UTI, nephropathy
Extrarenal cause:
• Preeclampsia, acute infection
• Leukemia, hyperthyroidism, fever
• MM (globulin is excreted)
Consequence of proteinuria:
1. Hypoalbuminemia & edema
2. Hypotonic hypervolemia
3. Hypercoagulability
4. Risk of infection
5. Loss of transport protein
6. Risk of drug toxicity
7. High risk of kernicterus
8. Hyperlipidemia
Proteinuria indicates the risk of :
• Renal disease
• CVD
• Nephropathy in diabetic pts
• End organ damage in hypertensive pts.
Edema:
Condition characterized by excess accumulation
of fluid in interstitial space
Causes of edema:
1. Cardiac cause: CCF
2. Renal cause: nephritis, NS, RF
3. Hepatic cause: CLD, LC, hepatic failure
4. Protein loosing enteropathies: Celiac disease,
ulcerative colitis, crohn’s disease.
5. Kwashiorkor
6. Lymphatic obstruction
7. Venous obstruction
8. misc: allergy, burn
Pathogenesis of edema:
Mechanism of edema:
1. Decrease COP:
• Hepatic disease
• Renal disease
• Protein loosing enteropathies
• kwashiorkor
2. Increased capillary hydrostatic pressure:
• CCF
• Renal failure
• Venous obstruction, DVT
• Lymphatic obstruction.
Increased capillary permeability:
• Inflammation
• Sepsis, burn
• Allergy
Renal function test:
Group of tests done to evaluate the function of
kidney is called RFT
Indication of renal function tests:
1. Diagnosis & prognosis of renal disease
2. Assessment of severity
3. DD of edema & proteinuria
4. EE & ABD
Categories of renal function test:
1. Urine RE
2. Evaluation of glomerular function
3. Evaluation of tubular function
Urine RE:
Physical examination: volume, specific gravity,
osmolarity, colour, appearace
Oliguria in renal failure
Polyuria in DI
Osmolarity & SP gravity decreases in acute renal
failure, nephrogenic DI
Chemical examination: PH , protein, glucose,
blood, KB, bile salt/pigment
PH changes in ATN
Protein increased in glomerular & tubular
dysfunction
Presence of glucose in absence of DM indicates
in proximal tubular dysfunction
Microscopic examination:
RBC & cast are found in glomerular & tubular
dysfunction
Evaluation of glomerular function:
1. Measurement of GFR: normal 125 ml/min
2. Serum creatinine: normal 0.7-1.4mg/dL
3. Blood urea: 15-40 mg/dL, BUN: 7-14 mg/dL
4. Renal clearance test: Ccr- 70-140 ml/min,
5. Detection of albumin in urine: albuminuria is
the earliest manifestation of glomerular
dysfunction
Evaluation tubular function:
1. Assessment of renal concentrating power:
• Water deprivation test.
2. Detection of low MW protein urine.
3. Detection of glycosuria in normal blood
concentration
Routinely done RFT:
• Urine RE
• eGFR
• S. creatinine
• Blood urea concentration
• Creatinine clearance test
Advantages of Ccr:
• Simple & inexpensive
• Less interference by extra renal factors.
• Not affected by diet/exercise
• Less fluctuation of s. cr
Disadvantage of Ccr:
• Overestimation of GFR
• Insensitive marker of renal function
Limitation of RFT:
• Blood urea is a poor guide to renal function
• Serum Cr is more reliable than urea, but S. cr
does not increase until more than 50% renal
function has been lost.
• Measurement of GFR by radioisotope is not
done routinely.
• Ccr overestimates GFR