Persistent proteinuria is the principal marker for kidney damage.
A strong independent association exists between urinary protein excretion and risk of death with and without diabetes.
Proteinuria is independently associated with mortality in patients with a low GFR.
Independent risk factor for cardiovascular disease.
Earliest sign of renal complications related to diabetes, obesity and metabolic syndrome.
Found in as many as 17% of selected populations but fewer than 2% of patients have serious and treatable urinary tract disorders.
Urinary protein excretion greater than 150 mg per day.
Only 25% of patients with proteinuria have reduced GFR, and a similar proportion of those with lower GFR have proteinuria (Garg AX).
Glomerular disease is the most common cause of pathologic proteinuria.
In most cases results from podocyte injury, which is the hallmark of adult minimal change disease, focal segmental glomerulosclerosis and membranous nephropathy.
The podocyte is a specialized cell of the glomerulous which helps prevent proteinuria by regulating the actin cytoskeleton in their foot processes.
Glomerular abnormalities alter the permeability of the glomerular basement membrane, resulting in urinary loss of albumin and immunoglobulins.
In a grossly bloody 24 hour urine collection approximately 500 mg of protein excreted can be attributed to protein from the blood.
Values above 300 mg/day can be detected by urinary dipstick testing.
Proteinuria:
1. Microalbuminuria 30-150 mg 2. Mild 150-500 mg 3. Moderate 500-1000 mg 4. Heavy 1000-3000 mg 5. Nephrotic range more than 3500 mg
Therapy to reduce or prevent it is highly desirable.
Occurs when the permeability of the glomerular capillary is increased.
Increased capillary permeability may be related to inflammatory injury from small blood vessel vasculitis or from autoimmune diseases.
More common forms of proteinuric renal disease are not associated with inflammation.
Anti-inflammatory agents such as corticosteroids, immune modulating agents such as cyclophosphamide and cyclosporine can be effective treatment for inflammatory and noninflammatory type of disease processes.
ACE inhibitors and angiotenisn receptor blockaers (ARBs) are used as monotherapoies to decrease proteinuria and delay renal disease progression.
Reduction in proteinuria slows progression of chronic renal diseae and correlates closely with a decline in GFR over time.
Albumin to creatinine ratio in urine is indpendently associated with an increased risk of death at all levels of GFR (O’hare MA).
In younger individuals the albumin to creatinine ratio in urine association with an increased risk is higher , but is attenuated at lower levels of estimated GFR (O’hare MA).
Both ACE inhibitors and ARBs retard the decline in GFR associated with proteinuria which suggests that the renin-angiotensin system plays a significant role in the pathogenesis of chronic renal disease.
Altered circadian pattern of BP is associated with higher levels of proteinuria.
Only 25% of patients with proteinuria have reduced GFR, and a similar proportion of those with lower GFR have proteinuria (Garg AX).
Proteinuria is an independent risk factor for progressive renal damage, and it’s reduction with antihypertensive medications, particularly ACE inhibitors or ARBs, reduces the rate of decline in the GFR both in diabetics or nondiabetics.
ARBs administered to hypertensive patients with type II diabetes, proteinuria, and chronic kidney disease resulted in significant reduction in the risk of progression of chronic kidney disease from 15-37%, cardiovascular events and death (Lweis EJ, Brenner BM).
Patients with proteinuria may have a shorter estimated life expectancy compared with their healthier counterparts.
Men and women with heavy proteinuria are expected to die 15.2 and 17.4 years earlier, respectively, than those without proteinuria (Turin TC et al).
In the above study each 5-year age group going up to 85, life expectancy was shorter for individuals with higher levels of proteinuria. Men consistently had a shorter life expectancy compared with women.