proteinuria in adults
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Proteinuria in Adults: A Diagnostic
ApproachDr.I.A.P.B.Illeperuma
15/07/2015
Bit of history…..
Hippocrates (400 B.C.) described bubbles on the surface of the urine as indicating kidney disease and a long illness.
Physiology Although the glomerular filtration coefficient of albumin is small, the
daily filtered load can be as much as 8 g. To prevent such massive losses of albumin, quantitative reabsorption
along the proximal tubules is accomplished by “receptor”-mediated endocytosis
Because of its size, albumin cannot leave the tubular lumen on the paracellular route across the tight junctions.
Furthermore, albumin is not cleaved in the tubular lumen and therefore does not cross the apical membrane of the proximal tubular cell in the form of free amino acids
Thus the only mechanism able to mediate albumin reabsorption is endocytosis.
Proteinuria
The presence of abnormal quantities of protein in the urine, which may indicate damage to the kidneys.
Normal urinary protein excretion - < 150mg/ 24 hours Of that
40% - Tamm – Horsfall proteins secreted by thick ascending limb of the loop of Henle
40% - Low molecular weight immunoglobulins (IgA), Urokinase, Peptide hormones
20% - Albumin Normal albumin excretion - < 30mg/ 24 hours
Proteinuria
Microalbuminuria – Albumin excretion 30 – 300mg/ 24 hours
Macroalbuminuria – Albumin excretion 300 – 3500mg/ 24 hours
Nephrotic range proteinuria – Albumin excretion > 3500mg / 24h
Isaac Sarrabat 1600; Physician examining a urine flask. (US National Library of Medicine)
Detecting and Quantifying Proteinuria
1.Urine dipstick test
Negative - Less than 10 mg per dL
Trace - 10 to 20 mg per dL
1+ - 30 mg per dL
2+ - 100 mg per dL
3+ - 300 mg per dL
4+ - 1,000 mg per dL
Detecting and Quantifying Proteinuria
2. Sulfosalicylic acid (SSA) turbidity test
The advantage of this easily performed test is its greater sensitivity for proteins such as Bence Jones
An equal amount of 3 percent SSA is added to that specimen of urine The acidification causes precipitation of protein in the sample (seen
as increasing turbidity), which is subjectively graded as trace,1+, 2+, 3+ or 4+
Detecting and Quantifying Proteinuria
3. Heat and Acetic Acid Test If turbidity develops add 1-2 drops of glacial acetic acid If turbidity is due to phosphate or carbonate precipitation, it will
disappear with acetic acidNegative : No cloudinessTrace: Barely visible cloudiness.1+ : Definite cloud without granular flocculation2+ : Heavy and granular cloud without granular flocculation3+ : Densed cloud with marked flocculation.4+ : Thick curdy precipitation and coagulation
Detecting and Quantifying Proteinuria
4. 24 hour urine protein excretion
5. Urine protein creatinine ratio Determined in a random urine specimen while the person carries on
normal activity Recent evidence indicates that the UPr/Cr ratio is more accurate than
the 24-hour urine protein measurement. Fortunately, the ratio is about the same numerically as the number of
grams of protein excreted in urine per day. Thus, a ratio of less than 0.2 is equivalent to 0.2 g of protein per day
Causes of proteinuria
Benign
1. Fever2. Strenuous exercise3. Acute illness4. Emotional stress5. Orthostatic proteinuria
Due to increased renal blood flow
Causes of proteinuria
False positives in dipstick testing1. Concentrated urine2. Alkaline urine (pH > 7)3. Gross hematuria4. Mucous5. Semen6. White cells
Pathological proteinuria
Glomerular – Due to increased capillary permeability of glomerulusGlomerulonephritides – Primary or secondary
Tubular – Due to decreased tubular reabsorption of filtered proteinsTubulo-interstitial diseases
Overflow – Due to increased production of low molecular weight proteins
Monoclonal gammopathies, Leukaemias, Lymphomas
Pathological proteinuria Glomerular
Primary Minimal change disease Idiopathic membranous GN
FSGS Membranoproliferative GN IgA nephropathy
Secondary DiabetesConnective tissue disorders – Lupus
nephritisInfection – Post streptococcal, Hep BMalignancy – Lymphoma, Lung cancer
Pathological proteinuria Tubular
Hypertensive nephrosclerosisUric acid nephropathyHeavy metalsSickle cell diseaseNSAIDSHypersensitive interstitial nephritis
OverflowHaemoglobinuria/MyoglobinuriaMyelomaAmyloidosis
Diagnostic Evaluation of Proteinuria1. When proteinuria is found on a dipstick urinalysis, the urinary
sediment should be examined microscopically MICROSCOPIC FINDING PATHOLOGIC PROCESSFatty casts, free fat or oval fat bodies
Nephrotic range proteinuria (> 3.5 g per 24 hours)
Leukocytes, leukocyte casts with bacteria
Urinary tract infection
Leukocytes, leukocyte casts without bacteria
Renal interstitial disease
Normal-shaped erythrocytes Suggestive of lower urinary tract lesion
Dysmorphic erythrocytes Suggestive of upper urinary tract lesion
Erythrocyte casts Glomerular diseaseWaxy, granular or cellular casts Advanced chronic renal disease
Eosinophiluria* Suggestive of drug-induced acute interstitial nephritis
Hyaline casts No renal disease; present with dehydration and with diuretic therapy
* A Wright’s stain of the urine specimen is necessary to detect eosinophiluria
Diagnostic Evaluation of Proteinuria
2. If urinary sediments are positive, investigate accordingly.3. Findings suggestive of infection on microscopic urinalysis mandate
antibiotic treatment and then repeated dipstick testing4. If the results of microscopic urinalysis are inconclusive and the
dipstick urinalysis shows trace to 2+ protein, the dipstick test should be repeated on a morning specimen at least twice during the next month
5. If a subsequent dipstick test result is negative, the patient has transient proteinuria, which is not associated with increased morbidity and mortality, a specific follow-up is not indicated.
Diagnostic Evaluation of Proteinuria
ORTHOSTATIC PROTEINURIA
This benign condition occurs in about 3 to 5 percent of adolescents and young adults which is characterized by increased protein excretion in the upright position but normal protein excretion when the patient is supine.
To diagnose orthostatic proteinuria, split urine specimens are obtained for comparison.
The first morning void is discarded and 16-hour daytime specimen is obtained with the patient performing normal activities and finishing the collection by voiding just before bedtime
An eight-hour overnight specimen is then collected. The daytime specimen typically has an increased concentration of
protein, with the nighttime specimen having a normal concentration.
ISOLATED PROTEINURIA
A proteinuric patient with normal renal function, no evidence of systemic disease that might cause renal malfunction, normal urinary sediment and normal blood pressures is considered to have isolated proteinuria.
Protein excretion is usually less than 2 g per day These patients have a 20 percent risk for renal insufficiency after 10
years and should be observed with blood pressure measurement, urinalysis and a creatinine clearance every six months
References
American family physician online - Proteinuria in Adults: A Diagnostic Approach
http://www.aafp.org/afp/2000/0915/p1333.html
Medscape online - Proteinuria: Background, Pathophysiology, Etiologyhttp://emedicine.medscape.com/article/238158-overview
Harrisons Principles of Internal Medicine,18th Edition
Thank you for
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