ProteinuriaIncreased protein in urine, leading to loss of protein. Normally, only a very small amount of protein is excreted in the urine. In chronic kidney disease, the amount lost may increase. High blood pressure damages blood vessels in the nephrons making them more permeable and... describes the excretion of proteins via the kidneys.
In proteinuria, proteins, mostly plasma proteins such as albumins and globulins, enter the urine. Protein excretion is usually not possible as proteins cannot pass through the filter apparatus, the glomerulus, due to their size and charge. If (smaller) proteins do pass through the filter apparatus, they are recovered in the subsequent tubular system and are therefore not excreted in the urine.
Loss of protein selectivity at the glomerular filter system
To understand the effects of proteinuria, it is helpful to have an understanding of the normal glomerular filtration barrier. The blood contains proteins involved in fluid balance and the transport of charged molecules. Plasma proteins such as albumins and globulins also exert what is called oncotic pressure, which ensures that fluid is retained in the blood and cannot pass into the tissues. Loss of plasma proteins can lead to water build-up in the tissues (oedemaExcess fluid collecting in the tissues of the body, which can cause them to become swollen....). It takes a lot of energy for the body to produce proteins, so the excretion and loss of these proteins would be a waste. The glomerular filtration barrier is designed to prevent the loss of these valuable proteins. The filter system in the glomerulus is therefore designed in such a way that albumins and globulins, which are large, negatively charged molecules, cannot pass through the filter. There are small proteins that can be filtered out. However, these are subsequently recovered in the cells of the proximal tubule (tubular system). Therefore, the presence of proteins in the urine is initially regarded as an unusual condition. The control and management of proteinuria is of great importance in the context of CKD.
Causes of proteinuria
Proteinuria can be caused by many different things. These can be classified as prerenal, i.e. causes that are independent of the kidneys, such as severe muscle or blood loss. Tumour processes or acute pancreatic diseases can also lead to proteinuria. In the case of prerenal causes of excessive protein excretion in the urine, proteins that are not normally present in the blood are filtered in the glomerulus.
Renal causes, i.e. those originating in the kidney itself, are pathological changes in the tubular system of the nephronsNephrone sind die Filtereinheiten der Nieren...., such as those caused by acute or chronic kidney inflammation, kidney toxins, leptospirosis, copper storage disease of the liver in Labrador retrievers and Fanconi syndrome. Pathological changes to the glomerulus (glomerulopathies) have tumorous, infectious and drug-related causes in addition to inflammatory processes and high blood pressure. Glomerulopathies can also occur in connection with certain breeds.
Postrenal causes located in the urogenital tract (ureter, bladder, uterus, etc.) are usually of an inflammatory nature or are associated with stone formation (urinary stones, bladder stones). Tumorous causes are also possible causes of postrenal proteinuria.
Increased protein excretion in the urine can occur when feeding a high-protein diet. Further urine tests for cells, bacteria and urinary stones are therefore recommended to clarify the diagnosis of proteinuria. Urine electrophoresis can help to identify the cause of proteinuria, as it can confirm the presence of large (high molecular weight) proteins.
Structure of the glomerular filtration apparatus
A. Healthy glomerulus: The filtering apparatus is the glomerulus, a tangle of blood vessels surrounded by sheaths such as Bowman’s capsule, which forms filter pores and acts as a sieve. It allows waste products to pass through the pores into the urine (passively) and at the same time retains important proteins and blood cells (= selective filter). The glomerulus forms a barrier for large molecules and/or charged molecules (e.g. plasma proteins) and thus prevents their loss via the urine.
B. Unhealthy glomerulus: If the glomerulus is damaged, the pores of the filter apparatus may be compromised and the membrane may no longer be negatively charged. This can lead to larger and/or negatively charged molecules, such as plasma proteins, being able to pass through the filter.
High blood pressure is directly related to this situation. Persistent high blood pressure results in alterations to the vessel walls in the glomerulus, which can consequently impact the filtration process. Additionally, elevated blood pressure is linked to an enhanced filtration rate, potentially leading to the filtration of proteins. If the kidney is damaged, these filtered proteins are no longer sufficiently recovered, so that more proteins appear in the urine and are therefore lost.
Consequences of proteinuria for kidney health
If more proteins pass through the glomerular filter, inflammatory processes occur in the subsequent tubular system due to the increased amount of proteins that need to be recovered, which, together with the changes in the glomerulus, lead to the progression of chronic kidney disease.
The protein overload of the cells of the proximal tubule, which are responsible for the recovery of proteins, activates a cascade of inflammatory and other mediators. This leads to inflammation, initially of the affected tubule cells, then of the kidney tissue and to the progression of renal fibrosis.
Consequences of protein loss for the cat
The loss of protein via the urine in connection with CKD is predominantly the result of the excretion of plasma proteins, namely albumin and globulin. These proteins are responsible for the so-called oncotic pressure in the blood, which is a prerequisite for maintaining the water content of the blood and preventing its leakage into tissues. Should the loss of albumin and globulin persist, the accumulation of fluid in tissues is a potential consequence, which may manifest as oedema and effusions. In addition, fluid loss can contribute to the development of hypertensionHigh blood pressure.. Furthermore, the loss of protein contributes to muscle wasting and weight loss, which in turn results in emaciation of the CKD cat.
Diagnosis of proteinuria
Protein loss via the kidneys is diagnosed using the UPC = urine protein to creatinineCreatinine is a breakdown product of muscle metabolism. Its blood level is dependent, among many factors, on age, weight, nutritional status and muscle mass. Hence, creatinine levels in the blood vary from individual to individual. Creatinine is continuously excreted in the urine. Increased blood creatinine... ratio. The UPC can therefore only be determined from a urine sample. The test measures the amount of protein and creatinine in the same urine sample and the difference between the two values is expressed as a ratio. The protein-creatinine ratio in urine, for example, measures whether protein excretion is higher than expected compared to creatinine excretion. If this is the case, proteinuria is present.
The protein/creatinine ratio should only be determined from urine samples that are free of blood, inflammatory cells and urinary stones/urinary sediment. To determine whether the sample is suitable for the protein-creatinine test, a complete urinalysis and sediment analysis is therefore carried out first. The reason for this is that the presence of blood and inflammatory cells can lead to a falsely high urine protein to creatinine ratio, which indicates kidney disease even though there is another cause.
It is recommended to repeat the protein-creatinine ratio (with complete urinalysis) in several consecutive urine samples (see IRIS stages). The longer the protein loss continues (persists), the more likely it is that serious kidney disease is present. Persistent proteinuria is proteinuria that has been detected in at least 3 urine tests at intervals of 2 or more weeks.
When kidney function is reduced and the urine cannot be concentrated sufficiently and becomes dilute (= the specific gravity of the urine decreases), traces of protein in the urine are sufficient to indicate chronic kidney disease.
UPC as a marker of improved renal function
If the proteinuria can be reduced with treatment, the progression of CKD will also be slowed down. In an animal with CKD, the urinary protein to creatinine ratio can also be used to monitor kidney function, e.g. to see if kidney function improves in response to treatment. This was achieved, for example, through the use of various antihypertensive drugs or a high-performance adsorber for the precursors of uraemic toxinsToxic, nitrogen-containing urinary substances responsible for uraemia and kidney damage.... in the intestine (see Treatment).
IRIS sub-stages proteinuria
The test for proteinuria is measured in urine using the urine protein to creatinine ratio, also known as the UPC. This urine test should be repeated after 10-14 days to check for persistent proteinuria.
CKD cats with a UPC > 0.4 have a 4-fold higher mortality risk than CKD cats with a UPC < 0.2.
Proteinuria can be treated with antihypertensive medication. More on this see Treatment.