From the Guidelines
Proteinuria should be quantified in glomerular disease, as it has disease-specific relevance for prognosis and treatment decision-making, according to the KDIGO 2021 clinical practice guideline for the management of glomerular diseases 1. When detected, patients should undergo further evaluation to determine the underlying cause and severity. Initial management includes blood pressure control with ACE inhibitors (like enalapril 5-20 mg daily or lisinopril 10-40 mg daily) or ARBs (such as losartan 25-100 mg daily), which reduce proteinuria and slow kidney disease progression. Lifestyle modifications are essential, including:
- Sodium restriction to less than 2 grams daily
- Moderate protein intake (0.8 g/kg/day)
- Regular exercise
- Weight management
- Smoking cessation
- Avoiding nephrotoxic medications like NSAIDs The severity of proteinuria is categorized as:
- Mild (150-500 mg/day)
- Moderate (500-3500 mg/day)
- Severe (>3500 mg/day) with nephrotic-range proteinuria (>3.5 g/day) requiring specialist care. Regular monitoring of urine protein levels, kidney function, and blood pressure is necessary to assess treatment effectiveness. Proteinuria occurs because damaged glomeruli in the kidneys allow proteins, particularly albumin, to leak into the urine instead of being retained in the bloodstream, disrupting the kidney's filtering mechanism and potentially leading to progressive kidney damage if left untreated. Under most circumstances, untimed urine samples should be used to detect and monitor proteinuria (level A recommendation) 1. It is usually not necessary to obtain a timed urine collection (overnight or 24-hour) to measure proteinuria (level A recommendation) 1. The ratio of protein or albumin to creatinine in an untimed urine specimen has replaced protein excretion in a 24-hour collection as the preferred method for measuring proteinuria 1. Using a ratio corrects for variations in urinary protein concentration due to hydration and is far more convenient than timed urine collections. The ratio of protein or albumin to creatinine in an untimed urine sample is an accurate estimate of the protein or albumin excretion rate 1. However, the most recent guideline from KDIGO in 2021 should be prioritized for management decisions 1.
From the FDA Drug Label
The secondary endpoints of the study were change in proteinuria, change in the rate of progression of renal disease, and the composite of morbidity and mortality from cardiovascular causes ... Compared with placebo, losartan significantly reduced proteinuria by an average of 34%, an effect that was evident within 3 months of starting therapy
- Proteinuria reduction: Losartan significantly reduced proteinuria by an average of 34% compared to placebo.
- Onset of effect: The effect of losartan on proteinuria reduction was evident within 3 months of starting therapy 2.
From the Research
Definition and Causes of Proteinuria
- Proteinuria is a common finding in adults in primary care practice, and it can be caused by various factors, including benign and serious disorders 3.
- Benign causes of proteinuria include fever, intense activity or exercise, dehydration, emotional stress, and acute illness, while more serious causes include glomerulonephritis and multiple myeloma 3.
- Proteinuria can also be associated with a renal or systemic disease, or it may be isolated, occurring in asymptomatic patients without evidence of any disease or abnormality of the urine sediment 4.
Evaluation and Diagnosis of Proteinuria
- An algorithmic approach can be used to differentiate benign causes of proteinuria from more serious disorders, and a quantitative measurement of urinary protein is often needed to evaluate the severity of proteinuria 3.
- The urine protein-to-creatinine ratio performed on a random specimen has many advantages over the 24-hour collection, primarily convenience and possibly accuracy 3.
- Patients with proteinuria greater than 2 g per day or in whom the underlying etiology remains unclear after a thorough medical evaluation should be referred to a nephrologist 3.
Pathophysiology and Treatment of Proteinuria
- Proteinuria is a key biomarker in nephrology, and it is central to diagnosis and risk assessment, as well as the primary target of many important therapies 5.
- Untreated proteinuria is strongly linked to progressive loss of kidney function and kidney failure, and excess protein reaching the renal tubules can activate inflammatory and fibrotic pathways, causing interstitial fibrosis and glomerulosclerosis 5.
- Several treatments, including angiotensin system blockade and statins, have been shown to effectively slow the progression of proteinuric chronic kidney disease, and a multimodal intervention may be required to afford renoprotection in overt diabetic nephropathy 6, 7.
Management of Proteinuria in Diabetic Patients
- Antihypertensive therapy with different types of drugs can reduce microalbuminuria or clinical proteinuria and retard the progression toward end-stage renal failure in diabetic patients 7.
- ACE inhibitors have been shown to have a greater renal protective effect than conventional therapy or calcium antagonists in diabetic patients with microalbuminuria or overt proteinuria 7.
- The addition of a statin to a combination of ACE inhibitor and ARB can normalize proteinuria in experimental diabetes and translate into full renoprotection 6.