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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