|Classification according to ICD-10|
|ICD-10 online (WHO version 2019)|
Under proteinuria is defined as the excessive excretion of proteins (protein) via the urine . The limit for normal ( physiological ) protein excretion is set at less than 150 milligrams per day. Increased protein excretion can be a harmless, temporary occurrence and is known as benign reversible proteinuria . However, persistently increased amounts of protein in the urine are not only the result of various diseases, but also an important independent cause of the progression of kidney disease .
For the first time scientifically proven protein in the urine (and thus the possibility of a reduced "protein tightness" of the kidneys) was in 1770 by Domenico Cotugno . An important function of the kidneys is to filter blood plasma, this takes place in the glomerula of the kidney corpuscles . Proteins with a molecular mass of 80 kilodaltons (kDa) or more - such as globulins - are retained by this “filter”. In contrast, substances up to a molecular mass of 6–15 kDa pass this barrier. In addition to this size selectivity, there is also a charge selectivity that retains strongly negatively charged proteins.
99.97% of albumin with its molecular mass of 66-69 kDa is retained. The sieving coefficient for albumins is thus less than 0.001. The reason is the strong negative charge of the albumin molecule, which prevents increased filtration . The glomerular filter is more permeable for molecules of the same size with no or even positive charge.
The proteins that get into the primary urine are divided into macromolecular and micromolecular proteins, the limit being drawn with albumin or its molecular mass. 96 percent of these proteins are reabsorbed in the proximal tubule . The uptake occurs through the mediation of the receptors of the Megalin-Cubilin complex as a specific, ATP -dependent endocytosis . Small amounts of proteins get into the terminal urine even under physiological conditions.
The causes of pathological proteinuria are changes that take place in the actual urine formation or have nothing to do with it itself. As renal forms, the former are divided into glomerular and tubular proteinuria, the latter into prerenal (or preglomerular) and postrenal forms.
The prerenal causes lead to an oversupply of proteins and thus to so-called overflow proteinuria . With these pathologically increased concentrations of (low molecular weight) proteins in the serum, there is consequently an increased filtration and an exceeding of the capacity for resorption of these proteins in the proximal tubule of the nephron .
A disorder localized in the glomerulum - usually inflammation ( glomerulonephritis ) - causes a more permeable filter, so that the absorption capacity in the tubule is also exceeded.
If the tubular cell function is impaired, the reabsorption of proteins is primarily impaired. Normal concentrations of proteins in primary urine also lead to significant proteinuria.
In postrenal disorders, the proteins come from the urinary tract .
If the amount of protein excreted in the urine is more than 3–3.5 g per 24 hours, in children more than 1 g per m² body surface and 24 hours, we speak of so-called major proteinuria . This usually leads to the development of a nephrotic syndrome .
The causes of proteinuria are:
- acute and chronic glomerulonephritis
- Metabolic disease such as diabetes mellitus
- Systemic diseases such as amyloidosis , systemic lupus erythematosus and the like a.
- cardiac and vascular causes, v. a. the arterial hypertension
- haematological diseases such as sickle cell anemia or multiple myeloma
- congenital diseases such as congenital nephrotic syndrome or Alport syndrome
- Pregnancy complications such as preeclampsia
- a kidney transplant
- a chronic transplant rejection
- Microorganisms , viruses , bone marrow inflammation
In addition to the amount, the composition of the proteins is also important. Even with minor proteinuria, a disease can be present if there is a pathological distribution pattern. This applies particularly to systemic diseases such as diabetes mellitus , arterial hypertension or lupus erythematosus .
The majority of the 500 proteins present in the urine of healthy people have not yet been identified, although more sensitive measurement methods such as radioimmunoassay or nephelometry can help.
The main urinary proteins are
- Albumin ,
- Globulins ( alpha-1 microglobulins and alpha-2 macroglobulins ),
- Uromodulin (= Tamm-Horsfall protein), the most important physiological protein produced in the kidneys,
- Antibody light chains ( kappa and lambda light chains ).
Albumin: Albumin can be excreted to an increased extent in the case of glomerular filtration disorders as well as in the absence of tubular reabsorption. A clinically isolated albumin excretion is referred to as albuminuria, while the minor albumin excretion that is not detectable with common urine strips, but clinically significant in the case of diabetes is called microalbuminuria .
People in whom an increased excretion of albumin in the urine is proven have an increased risk of a progressive loss of kidney function up to and including dialysis-dependent kidney failure . Given kidney function, the higher the proteinuria, the higher the mortality and the risk of heart attack . The Leiden physician Frederik Dekkers (1648–1720) recognized the milky cloudiness of the protein-rich urine after boiling and adding acetic acid. The Italian Domenico Cotugno (1736–1822) also carried out a detection of albumin in the urine of "water addicts" brought about by heat precipitation. Proteinuria, which occurs together with edema, was then established in 1827 by Richard Bright (1789–1857) as an important diagnostic criterion.
- ↑ Klahr S, Schreiner G, Ichikawa I .: The progression of renal disease . In: N Engl J Med . 318, No. 25, 1988, pp. 1657-66. PMID 3287163 .
- ↑ Joachim Frey : Diseases of the kidneys, the water and salt balance, the urinary tract and the male sexual organs. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition ibid. 1961, pp. 893-996, here: pp. 910-912.
- ↑ Klinke, Silbernagl: Textbook of Physiology . 4th edition, Georg Thieme Verlag, Stuttgart 2004, ISBN 3-13-796004-5 , p. 300f.
- ↑ Proteinuria (nephrotic syndrome) . ( Memento of the original from December 8, 2015 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. Medical University of Vienna - AKH Consilium
- ↑ virtual medical-analytical laboratory, urine results: proteins ( Memento from June 7, 2007 in the Internet Archive ) Biorama
- ↑ Jürgen E. Scherberich: Non-invasive Diagnosis of Kidney Diseases - Differential Clinical Evaluation of the Forms of Proteinuria ( Memento of the original from September 14, 2013 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice.
- ↑ Marije van der Velde, et al .: Screening for albuminuria identifies individuals at increased renal risk . In: Journal of the American Society of Nephrology . 20, No. 4, April 2009, ISSN 1533-3450 , pp. 852-862. doi : 10.1681 / ASN.2008060655 . PMID 19211710 .
- ↑ Kunihiro Matsushita, et al .: Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis . In: The Lancet . 375, No. 9731, June 12, 2010, ISSN 1474-547X , pp. 2073-2081. doi : 10.1016 / S0140-6736 (10) 60674-5 . PMID 20483451 .
- ↑ Brenda R Hemmelgarn, et al .: Relation between kidney function, proteinuria, and adverse outcomes . In: JAMA: The Journal of the American Medical Association . 303, No. 5, February 3, 2010, ISSN 1538-3598 , pp. 423-429. doi : 10.1001 / jama.2010.39 . PMID 20124537 .
- ^ FP Schena: The role of Domenico Cotugno in the history of proteinuria. In: Nephrol. Dialysis Transplant. , Volume 9, 1994, pp. 1344 f.
- ↑ Horst Kremling: On the development of kidney diagnostics. In: Würzburger medical history reports 8, 1990, pp. 27–32; here: p. 28.