From the meeting

“Le Proteine: dal Laboratorio alla Clinica”

“Proteins: from the Laboratory to the Clinic”
X Edition - Castrocaro, 24th – 26th October, 2001
Organised by CEFAR – Centro Europeo per la Formazione e la Ricerca in Scienze Sanitarie e in Biotecnologie
Patron: SIBioC – Società Italiana di Biochimica Clinica e Biologia Molecolare Clinica

Proteinuria – Diagnostics and Interpretation with

Marker Proteins
Computerising Processing and report (”MDI–LabLink”)

Werner H. Siede a, Axel Regeniterb

a) Presenting Author: Central Laboratory, Klinikum Lippe-Lemgo, Lemgo, Germany
b) Author for correspondence: Central Laboratory, Kantonsspital Basel, Switzerland - Fax +41 61 265 4600
E-mail: [email protected]

Index
Introduction
Pathophysiology
Pre-analytical considerations
Analytical considerations
Diagnostic strategy
Data Presentation and Interpretation
Indications and Applications
Figures

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Proteinuria – Diagnostic and Interpratation with Marker Proteins W.H. Siede a, A. Regeniterb

Non standard abbreviations

BJP Bence Jones Proteins ALB Albumin
BJ Bence Jones TRF Transferrin
FRL Free Light Chains A1M Alfa-1 microglobulin
FRL-K Free Light Chains kappa A2M Alfa-2 macroglobulin
FRL-L Free Light Chains lambda IGG Immunoglobulins IgG
IFE Immunofixation IGM Immunoglobulins IgM
RBP Retinol binding protein
B2M Beta-2 microglobulin

Key Words
Glomerular proteinuria, Tubular proteinuria, Bence Jones Protein, Kappa Free Light Chains, Lambda Free Light
Chains

(molecular weight). Groups of proteins within a certain

Introduction molecular weight range are affected similarly.
The development of immunological assays for specific In SDS-PAGE, the traditional technique to identify
proteins in urine has led to considerable improvement patterns of proteinuria, proteins are separated strictly
in the early detection, prognostic evaluation and according to their molecular weight. Single proteins can
therapeutic monitoring of kidney and urinary tract then be identified within these patterns. They serve as
diseases. marker proteins for typical pathobiochemical conditions
Basic urine examination by test strips and/or (Fig. 2) (1 – 8).
microscopy should be supplemented with a sensitive The glomerular filtration of proteins depends on two
and quantitative determination of total protein or different functional properties of the glomerular basal
principal urinary marker proteins like albumin and membrane. Larger proteins (e.g. IgG, 150 kdal) are
alpha-1-microglobulin. restricted from filtration simply by pore width.
Complete differential diagnosis can be accomplished by Smaller Proteins of a size range that allow them to just
measuring only a few marker proteins. This replaces pass through the glomerular pores (e.g. albumin, 67
the solely qualitative evaluation of protein patterns with kdal, and transferrin 90 kdal) are repelled effectively by
laborious SDS-PAGE. negatively charged molecules in the membrane
This article reviews the work-up of proteinuria. („anionic filter“) since these proteins are also negatively
It covers pathophysiology, analytical and pre-analytical charged at a physiological blood pH.
considerations, the diagnostic strategy, data Therefore, proteinuria is observed not only in structural
presentation and interpretation, medical indications and changes of the basal membrane (“unselective
its applications. glomerular proteinuria”), but also in potentially
reversible conditions with loss of the glomerular
Pathophysiology anionic filter function.
The nephron is the functional unit within the kidney. It This condition is characterized by a “selective
consists of two main structures, the glomerulum and glomerular proteinuria” pattern (e.g.
tubulus. In the glomerulum, filtration produces the microalbuminuria, minimal change nephritis).
primary urine; while the concentration and reabsorption Proteins with a lower molecular weight of albumin
of small proteins takes place in the tubular system. pass freely through the glomerular basal membrane and
Functional and structural defects of one or both of these are physiologically reabsorbed within the tubular
parts lead to various and distinct patterns of proteinuria system.
(Fig. 1). However, protein reabsorption is a highly energy-
The principal reason for the different protein handling consuming process. In addition, its transport capacity. is
by glomerulum and tubulus is molecular size limited It is therefore easily disturbed by even minor
factors (e.g. fever, medication).

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Proteinuria – Diagnostic and Interpratation with Marker Proteins W.H. Siede a, A. Regeniterb

An extremely sensitive indicator for the resulting Analytical considerations

pattern of “incomplete tubular proteinuria” is alpha-1-
microglobulin (33 kdal). The concentrations of proteins range from just above
Severe tubular damage leads to further structural the reference range limit in early renal damage to
changes (nephrotoxicity of drugs, progressive renal extremely high amounts in patients with nephrotic
diseases) and a disturbed tubular reabsorption of even syndrome.
very small proteins. These proteins, for example retinol- The immunological measurement of marker proteins by
binding protein (21 kdal) or beta-2-micro-globulin (12 nephelometry is well suited for this situation.
kdal) are then measurable in urine:and form the pattern The instruments provide the maximum analytical
of “complete tubular proteinuria”. sensitivity required to measure proteins that have upper
Primary glomerular defects effect the tubulo- reference ranges near or even below 1 mg/g creatinine
interstitium and vice versa, since the three dimensional (e.g. transferrin, retinol-binding protein, beta-2-
structure of nephrons is closely interwoven. Mixed microgloblin, kappa, lambda light chains).
forms of glomerular/tubular patterns are therefore They are also able to correctly handle antigen excess
common in advanced forms of renal disease. situations, which occur frequently in proteinuria
The frequently symptomless and often underestimated samples.
involvement of the tubulo-interstitium is the critical The correct total protein determination in urine proves
component in the final outcome of kidney diseases. to be especially difficult.
Tubulo-interstitial protein markers reflect these changes The upper reference range limit of healthy individuals
and indicate the prognosis (Fig. 10 ) (9, 24 – 26). is somewhere between 100-120 mg/g creatinine.
Post-renal (strictly: post-glomerular) affections with or Conventional brands of dipsticks are therefore limited
without hematuria add unfiltered serum proteins to the to the detection of advanced renal affections. They are
urine. Thus, they mimic glomerular or mixed types of not suited for the exclusion of kidney disease. Their
proteinuria. The post-renal addition of proteins can be detection limit far exceeds the upper normal reference
identified by the urinary presence of very large range and lies somewhere between 150 and 300 mg/l.
molecules (e.g. alpha-2-macroglobulin (720 kdal), IgM, Furthermore, they measure mostly albumin. Smaller
Apolipoprotein A) Even in advanced glomerular molecules, as seen in mainly tubular or prerenal
disease, these molecules are almost completely proteinuria (free kappa or lambda light chains) are
restricted from glomerular filtration. detected to a much lesser extent or not at all.
Pre-renal (overflow) proteinuria is characterized by a The detection limit of the standard photometric protein
large production of smaller proteins that is excessively determination methods (e.g. Biuret) is also too
contributed to serum. Due to their small size, these unsensitive.
molecules pass the glomerulum freely. However, the Methods using pyrogallol-red or benzethonium-choride
quantity of these proteins exceeds the protein offer an acceptable compromise (20 – 22) with a
reabsorption capacity of the tubular part of the kidney. detection limit of 40 - 60 mg/l. They are therefore able
Thus, they appear in urine. The most frequent type of to measure within the upper reference range of healthy
pre-renal proteinuria is the appearance of free individuals. In addition, they can be automated.
monoclonal light chains (Bence Jones protein). A
longer existing conditions of overflow proteinuria will
Diagnostic strategy
damage the tubular system, which can again be assessed The diagnostic strategy is outlined schematically in Fig.
by urinary marker proteins effectively (10, 11). 4.
It represents the stepwise diagnostics (SCREENING,
Pre-analytical considerations DIFFERENTIATION, CONFIRMATION) of all types
Sampling conditions are extremely important for a of proteinuria (GLOMERULAR, TUBULAR,
correct determination of urinary proteins. 24 hour timed POSTRENAL, PRERENAL) with respect to a rational,
urine samples and also samples collected as first cost-effective reflex testing strategy.
morning urine have several drawbacks. The material of All patients are screened using dipsticks for
choice for the determination of almost all urinary erythrocytes/hemoglobin and leukocytes and total
parameters is the second morning urine (Fig. 3)(4, 12 – protein (pyrogallol-red or benzethonium-chloride
16). methods) is determined by photometer. All measured
Nevertheless, the variations in diuresis have to be proteins are referred to the creatinine content of the
corrected. All protein measurements must therefore be sample.
related to the creatinine concentration of the sample and If the protein concentration is below the upper reference
are expressed as mg/g creatinine (or alternatively as limit of 100 to 120 mg/g creatinine, a diagnostic
mg/mmol creatinine). relevant proteinuria is most unlikely, provided no other
Also, typical characteristics of individual proteins may indications for renal diseases or diseases with renal
influence their value as a marker protein . For instance, involvement are present.
beta-2-microglobulin is very unstable at acidic urine pH However, a considerable percentage of patients with
and therefore not an ideal marker protein (17 – 19). risk factors (e.g. diabetes mellitus, hypertension) show

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Proteinuria – Diagnostic and Interpratation with Marker Proteins W.H. Siede a, A. Regeniterb

elevated concentrations of either albumin or alpha-1- Data Presentation and Interpretation

microglobulin despite a total protein concentration
within the reference range. The interpretation of urinary protein patterns requires
In these cases as well as in all samples with a total the calculation of numerous ratios and formulas, based
protein concentration in the 100 to 300 mg/g creatinine on the fundamental work by Hofmann and Guder (4, 5).
range, the most sensitive and specific marker proteins Knowledge-based systems („expert systems“) on a
for glomerular and tubular function should be Personal computer, like MDI LabLink, are used with
measured; albumin and alpha-1-microglobulin. great success for calculation, interpretation of
If one of these proteins is elevated, further proteinuria patterns and vivid data presentation (Fig. 5)
differentiation with additional marker proteins is (6, 7).
necessary for the complete differentiation and The graphic presentation of the protein markers needs a
classification of proteinuria common denominator. However, laboratory values
This initial step can be omitted in patients with a total referring to the same organ system differ in their units
protein above 300 mg/g creatinine. In these samples of measurement as well as in their reference ranges.
additional proteins are elevated regularly. The values are comparable if they are divided by and
The complete work-up of proteinuria requires the expressed as multiple of their upper reference
measurement of transferrin and IgG for glomerular [LM1]limit.
proteinuria, retinol-binding protein and/or beta-2- The creatinine adjusted urinary proteins are then
microglobulin for tubular proteinuria. ordered according to their molecular weight and plotted
In samples with hematuria, alpha-2-macroglobulin is against a schematic nephron. Reference range proteins
used additionally to identify or rule out post-renal are indicated by a blue bar, elevated proteins with a red
contamination (4). one.
Evidence for pre-renal proteinuria is a larger than usual The proteins now form distinct patterns displaying the
gap between the total protein concentration and the sum patho-biochemical lesion – Fig. 6: measured proteins in
of the main marker proteins (23). urine, from top to bottom:
This is seen frequently in Bence-Jones proteinuria, i) Alpha-2-macroglobulin (exclusion of post-renal
which subsequently can be confirmed or excluded with contamination);
the ratio of free kappa to lambda light chains or ii) IgG, transferrin, albumin (glomerular markers);
immunofixation electrophoresis. iii) Alpha-1-microglobulin, retinol-binding protein
In general, the determination of free light chains is a (tubular markers).
very suitable screening test for Bence-Jones protein. The graph allows nearly instant recognition („signature
Nephelometric assays with sufficient analytical pattern“) of the underlying type of proteinuria and the
sensitivity (detection limit 5 mg/l) are available. In localization of the defect. This is most vividly evident
normal urine the concentration of light chains is below in the original color printout (Fig. 7).
the detection limit. Besides Bence-Jones proteinuria, The data is also presented numerically and an additional
elevated values are regularly found in tubular text interpretation classifies the defect.
proteinuria. Free light chains in tubular proteinuria are The interpretation text stems from MDI Lablink’s
of polyclonal origin and their increase is due to the interpretation module. The pattern of the sample is
tubular reabsorption defect. compared with patterns stored in a database. The
Bence-Jones proteinuria, in contrast, is an “overflow- database is freely accessible, so that the user maintains
proteinuria” caused by an overproduction of complete control over program function and output.
monoclonal free light chains. The kappa/lambda ratio Pattern definitions as well as interpretation texts can be
is either above or below the reference range e of 1 – 3,7 changed, deleted or added.
(28). The interpretation texts in the printout can be tailored
Immunofixation electrophoresis is used for with little effort for different information needs.
confirmation in these cases. Its value, however, is The output always contains text to describe the patho-
limited due to a lack of analytical sensitivity (detection biochemical classification of proteinuria, proposes
limit variable between 20 – 50 mg/l). ). additional tests („reflex testing“) and comments on the
Concentrating urinary samples cannot be validity of the result according to the built in algorithms
recommended, since artefacts are often produced for plausibility control (e.g. in samples with extreme
(“ladder phenomenon”)(29, 30). creatinine concentrations, unusual IgG concentrations,
A free kappa/lambda ratio in the range of 1 – 3,7 rules contamination with erythrocytes or leukocytes). It can
out Bence-Jones proteinuria almost completely (28), be tailored to additionally cite examples of typical
costly immunofixation electrophoresis is unnecessary diseases observed with the respective pattern.
and can be avoided in a large number of patients. The follow-up printout (Fig. 8) comments and presents
This diagnostic strategy in the work-up of proteinuria changes in marker protein concentrations tabularly and
leaves only few samples with rare and unusual graphically. It monitors disease progression and effects
constellations for further work-up with SDS-PAGE. of therapy .

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Proteinuria – Diagnostic and Interpratation with Marker Proteins W.H. Siede a, A. Regeniterb

Indications and Applications urinary patterns with MDI LABLINK: a statistical

evaluation. Clin Chim Acta 2000;297:261-73.
Indications for urinary protein differentiation according 8. Regeniter A, Nickeleit V, Dickenmann M,
to Scherberich are summarized in Fig. 9[LM2]. This Frischmuth N, Siede WH, Huber P et al. Specific
includes several laboratory result constellations, clinical Urine Protein Markers Indicate Histological
conditions, symptoms and diseases with a common Changes in Kidney Allografts. XXI. World
kidney involvement. It is supplemented by Fig. 10[LM3]. Congress of Pathology and Laboratory Medicine,
Here, a review of the principal applications for urinary (WASPALM) Duesseldorf, November 20-23 2001.
marker proteins in early detection and therapeutic Clin Lab 2001;47:622.
monitoring can be found. 9. Bernard AM, Vyskocil AA, Mahieu P, Lauwerys
Besides glomerular proteinuria, e.g. RR. Assessment of urinary retinol-binding protein
“microalbuminuria” in patients with diabetes and as an index of proximal tubular injury. Clin Chem
hypertension, tubular proteinuria is of special interest, 1987;33:775-9.
since the involvement of the tubulo-interstitium is often 10. Zappasodi P, Pascutto C, Bosoni T, Corso A.
the critical component in the final outcome of kidney Urinary proteins in multiple myeloma: strong
diseases. correlation with the indices of tumor burden.
Prognostic significance has been emphasized recently Haematologica 2001;86:878.
for retinol binding protein (24 –26), but also for IgG 11. Corso A, Serricchio G, Zappasodi P, Klersy C,
and Alpha-1-Microglobulin (27). Bosoni T, Moratti R et al. Assessment of renal
function in patients with multiple myeloma: the
In conclusion, we would like to emphasize the role of urinary proteins. Ann Hematol
extraordinary importance of quantitative protein marker 1999;78:371-5.
determination in urine as a decisive and integral part 12. Torng S, Rigatto C, Rush DN, Nickerson P, Jeffery
for diagnosis and therapeutic monitoring of often JR. The urine protein to creatinine ratio (P/C) as a
asymptomatic kidney disease. predictor of 24-hour urine protein excretion in
renal transplant patients. Transplantation
2001;72:1453-6.
References 13. Ginsberg JM, Chang BS, Matarese RA, Garella S.
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2. Boesken WH, Rohrbach R, Schollmeyer P. Quantification of proteinuria: a re-evaluation of the
Vergleich von Histologie und Urinproteinanalyse protein/creatinine ratio for elderly subjects. Age
(SDS-PAA-Discelektrophorese) bei Ageing 1993;22:443-9.
Nierenerkrankungen. Nieren und Hochdruckkrh 15. Bisaz E, Bianchetti MG, Donati R, Peheim E,
1978;5:206-14. Colombo JP, Oetliker OH. [Simplified
3. Boesken WH. Diagnostic significance of SDS- determination of proteinuria in children using a
PAA-electrophoresis of urinary proteins: different single urine sample]. Klin Padiatr 1994;206:387-
forms of proteinuria and their correlation to renal 91.
diseases. Curr Probl Clin Biochem 1979;235-48. 16. Steinhauslin F, Wauters JP. Quantitation of
4. Hofmann W, Rossmuller B, Guder WG, Edel HH. proteinuria in kidney transplant patients: accuracy
A new strategy for characterizing proteinuria and of the urinary protein/creatinine ratio. Clin Nephrol
haematuria from a single pattern of defined 1995;43:110-5.
proteins in urine. Eur J Clin Chem Clin Biochem 17. Davey PG, Gosling P. beta 2-Microglobulin
1992;30:707-12. instability in pathological urine. Clin Chem
5. Hofmann W, Sedlmeir-Hofmann C:, Ivandic M, 1982;28:1330-3.
Schmidt D, Guder WG, Edel HH. Befundung von 18. Donaldson MD, Chambers RE, Woolridge MW,
Urin-Protein-Mustern auf der Basis klinisch Whicher JT. Stability of alpha 1-microglobulin,
gesicherter Patientenkollektive. Typische Beispiele beta 2-microglobulin and retinol binding protein in
mit Textbefunden. Assesment of urinary-protein urine. Clin Chim Acta 1989;179:73-7.
patterns on the basis of clinically characterized 19. Blumsohn A, Morris BW, Griffiths H, Ramsey CF.
patients. Typical examples with reports. Lab med Stability of beta 2-microglobulin and retinol
1993;17:502-12. binding protein at different values of pH and
6. Regeniter A, Siede WH, Seiffert UB. Computer temperature in normal and pathological urine. Clin
assisted interpretation of laboratory test data with Chim Acta 1991;195:133-7.
'MDI- LabLink'. Clin Chim Acta 1996;248:107-18. 20. Watanabe N, Kamei S, Ohkubo A, Yamanaka M,
7. Regeniter A, Siede WH, Scholer A, Huber P, Ohsawa S, Makino K, Tokuda K. Urinary protein
Frischmuth N, Steiger JU. Interpreting complex as measured with a pyrogallol red-molybdate

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complex, manually and in a Hitachi 726 automated 26. Camara NO, Matos AC, Rodrigues DA, Pereira
analyzer. Clin Chem 1986;32:1551-4. AB, Pacheco-Silva A. Early detection of heart
21. Orsonneau JL, Douet P, Massoubre C, transplant patients with increased risk of
Lustenberger P, Bernard S. An improved ciclosporin nephrotoxicity. Lancet 2001;357:856-7.
pyrogallol red-molybdate method for determining 27. Bazzi C, Petrini C, Rizza V, Arrigo G, Beltrame A,
total urinary protein. Clin Chem 1989;35:2233-6. Pisano L, D'Amico G. Urinary excretion of IgG
22. Macart M, Forzy G, Gerbaut L, Vekich AJ, and alpha(1)-microglobulin predicts clinical course
Guilbaud JC. Measuring urinary protein with the better than extent of proteinuria in membranous
new BioRad reagent kit: evaluation and nephropathy. Am J Kidney Dis 2001;38:240-8.
comparison with five other methods. Ann Biol Clin 28. Regeniter A, Siede WH. Determination of free
(Paris) 1994;52:355-60. light chains as screening test for Bence-Jones
23. Boege F, Koehler B, Liebermann F. Identification proteinuria (submitted for publication).
and quantification of Bence-Jones proteinuria by 29. Harrison HH. The „ladder light chain“ or „pseudo-
automated nephelometric screening. J Clin Chem oligoclonal“ pattern in urinary immunofixation
Clin Biochem 1990;28:37-42. electrophoresis (IFE) studies: a distinctive IFE
24. Camara NO, Nishida S, Silva MS, Pestana JO, pattern and an explanatory hypothesis relating it to
Pereira AB, Sesso R, Pacheco-Silva A. Monitoring free polyclonal light chains. Clin Chem
serum beta-2 microglobulin is useful for detecting 1991;37:1559-64.
patients with increased risk of acute rejection 30. MacNamara EM, Aguzzi F, Petrini C, Higginson J,
during reduction in immunosuppression. Gasparro C, Bergami MR, Bianchi G, Whicher JT.
Transplant Proc 1998;30:4158-9. Restricted electrophoretic heterogeneity of
25. Camara NO, Matos AC, Rodrigues DA, Pereira immunoglobulin light chains in urine: a cause for
AB, Pacheco-Silva A. Urinary retinol binding confusion with Bence-Jones protein. Clin Chem
protein is a good marker of progressive 1991;37:1570-4.
cyclosporine nephrotoxicity after heart
transplant. Transplant Proc 2001;33:2129-31.

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Proteinuria – Diagnostic and Interpratation with Marker Proteins W.H. Siede a, A. Regeniterb

Figure 1

Proteinuria - Pathobiochemical Classification

X renal proteinuria
X selective

X moderately selective
X glomerular
X unselective

X incomplete
X tubular
X complete

X mixed glomerular/tubular

X prerenal proteinuria X myoglobinuria/hemoglobinuria

(“Overflow proteinuria“) X Bence-Jones-proteinuria
X ß-2-microglobulinuria

· postrenal proteinuria X postrenal hematuria

X urinary tract infection

Figure 2

Proteinuria - Marker Proteins

W Total protein W general marker
plausibility control
W Albumin W generell marker
glomerular proteinuria
X Transferrin X glomerular selectivity
X Immunoglobulin G X glomerular selectivity
urinary tract infection
postrenal proteinuria /hematuria
O alpha-1-microglobulin O tubulo-interstitial proteinuria
O Retinolbind. protein O tubulo-interstitial proteinuria
(complete)
O ßeta-2-microglobulin O tubulo-interstitial proteinuria
(complete)
V light chains (Kappa, Lambda) V Bence Jones / tubular proteinuria
Q alpha-2-macroglobulin Q postrenal proteinuria / hematuria

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Proteinuria – Diagnostic and Interpratation with Marker Proteins W.H. Siede a, A. Regeniterb

Figura 3

TP >300 mg/g crea

Screening Creatinine
Total Protein
Erythrocytes
Leukocytes
TP <300 mg/g crea
G
L
T
Global-
O Albumin α-1-microglobulin
M U
B
E
R U
elevated elevated L
U
L A
Special- Transferrin retinolbind.protein R
A and / or
R IgG ß-2-microglobulin

Differentiation
P Inter-
O pretation P
S Ery ≥ ++ Alb + α1+ IgG R
T Alb≥ 100 mg/g crea TP (> 300 mg/g crea) E
R < 0.3 (0.1) R
E E
N N
A A
L L
α-2- Kappa, Lambda,
Confirmation macroglobulin negative Immunfixation
SDS PAGE

Figure 4

2. Morning Urine
· The second urination in the morning,
approximately 2 hours after the first

X Close correlation to 24h collections (creatinine reference)

X Easily and reliably obtainable compared to timed (24h, 12h) samples
X Especially suited for a Doctor‘s office
X Suitable nearly for all urinary analytes
X Dipstick results (erythrocytes, leucocytes)

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Proteinuria – Diagnostic and Interpratation with Marker Proteins W.H. Siede a, A. Regeniterb

Figure 5

MDI LabLink Advantages

X Windows
X easy to use
X ODBC- interface
X individually configurable
X Instant graphic recognition
X Interpretation
X pathobiochemical classification
X proposal of additional tests
(„reflex testing“)
X Visualisation
X pathobiochemical defect
X damage quantification
X Followup

Figure 6

Patterns of Proteinuria
normal tubular incomplete tubular complete

glomerular selective glomerular unselective contamination postrenal

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Proteinuria – Diagnostic and Interpratation with Marker Proteins W.H. Siede a, A. Regeniterb

Figure 7

Figure 8

Followup

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Proteinuria – Diagnostic and Interpratation with Marker Proteins W.H. Siede a, A. Regeniterb

Figure 9

The following symptoms and diseases are indicative for a

urinary protein differentiation :
• Proteinuria
• Microhematuria
• Leucocyturia with or without bacterial infection
• normoglycemic glucosuria
• inexplainable renal insufficiency with or without proteinuria;
serum creatinine >1,4 mg/dl
• hypertonus; " inexplainable edema"
• Systemic rheumatic diseases where renal involvement is common
• Diabetes mellitus
• Nephrotoxic drugs (non-steroidal antiphlogistics, ACE-inhibitors, antibiotics,
cytostatica, Cyclosporin A, X-Ray contrast media
• Infections (streptococci, HBV, HIV, malaria etc.)
• Kidney stone carriers; hypopotassemia; hypercalcemia; hypophosphatemia
• EPH-Gestosis
• Renal allograft recipients

Figure 10

Applications for quantitative measurement

of urinary marker proteins
• Early detection of
• glomerular proteinuria (microalbuminuria)
• diabetes mellitus
• hypertension
• systemic rheumatic diseases
• EPH-Gestosis
• tubular proteinuria
• nephrotoxicity
• prerenal proteinuria
• monoclonal light chains (Bence Jones protein)
• Therapeutic monitoring
• Steroids / ACE inhibitors in selective / moderately selective glomerular proteinuria
• glomerular proteinurias („nephrotic syndrome“)
• Renal allograft recipients
• Prognostic Significance
• retinol binding protein (complete tubular proteinuria)
• alpha-1-microglobulin (cut-off 33.5 mg / g creatinine)
• IgG (cut-off 110 mg / g creatinine)

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