From the Guidelines
Proteinuria is primarily caused by conditions that damage the kidneys' filtering system, such as diabetes, hypertension, and glomerulonephritis, which can lead to significant morbidity and mortality if left untreated. The causes of proteinuria can be categorized into several groups, including:
- Diabetes and hypertension, which are the most common causes of proteinuria, as they gradually damage the glomeruli over time 1
- Glomerulonephritis, an inflammation of the kidney filters, which can result from infections, autoimmune diseases, or medications
- Other conditions such as multiple myeloma, amyloidosis, and certain medications like NSAIDs and some antibiotics
- Temporary proteinuria, which may occur with fever, dehydration, emotional stress, or intense exercise
- Orthostatic proteinuria, seen mainly in young adults, which happens only when standing
- Preeclampsia during pregnancy, which can also cause protein in urine
- Congenital conditions like Alport syndrome or polycystic kidney disease, which may lead to proteinuria It is essential to note that the severity of proteinuria varies from mild (microalbuminuria) to severe (nephrotic syndrome), with the latter causing significant protein loss, edema, and increased infection risk 1. According to the National Kidney Foundation practice guidelines, persistently increased protein excretion is usually a marker of kidney damage, and measurement of proteinuria is crucial for detecting and monitoring kidney disease 1.
From the Research
Causes of Proteinuria
- Proteinuria is a hallmark of diabetic nephropathy, and its development is closely linked to the progression of diabetic glomerulopathy 2, 3
- The degree of proteinuria correlates with the progression of glomerulosclerosis and tubulointerstitial fibrosis 3
- Hemodynamic changes, loss of negatively charged proteoglycans in the glomerular basement membrane (GBM), and podocytopathy are important mediators of proteinuria 3
- Components of the diabetic milieu, such as high glucose, accumulation of glycated proteins, high intrarenal angiotensin II (ANG II), and hypertension-induced mechanical stress, contribute to the development of proteinuria 3
- Activation of cytokine systems, including transforming growth factor-beta1 (TGF-beta1) and vascular endothelial growth factor-A (VEGF-A), plays a crucial role in the development of proteinuria 3
Mechanisms of Proteinuria
- Proteinuria is not only a marker of kidney damage but also exacerbates it through various mechanisms involving the glomerular and tubulointerstitial compartments 4
- The integrity of the glomerular filtration barrier maintains protein excretion below 150 mg/day, and damage to this barrier leads to proteinuria 4
- Podocyte injury, characterized by decreased podocyte number and/or density, GBM thickening, and altered matrix composition, correlates closely with the development and progression of albuminuria 3
- ANG II-stimulated podocyte-derived VEGF, through a novel autocrine signaling loop, appears to be a major cause of nephrin downregulation and the development of proteinuria 3
Treatment and Prevention
- Good control of hyperglycemia and hypertension, and maximal inhibition of ANG II, are essential steps in preventing the development and progression of diabetic nephropathy 3, 5
- Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are cornerstone treatments for reducing proteinuria 4, 5
- Recent advancements include sodium-glucose cotransporter 2 inhibitors, Finerenone, and dual inhibition of angiotensin II and endothelin-1 receptors, which offer renoprotective properties and anti-inflammatory and antifibrotic benefits 4