From the Guidelines
Patients with normal eGFR and proteinuria should be treated with ACE inhibitors or ARBs to reduce proteinuria and slow disease progression, with a target proteinuria level of less than 1 g/day. The presence of proteinuria in the urine, despite a normal eGFR, indicates kidney damage and requires prompt evaluation and management 1. The initial approach includes quantifying the proteinuria and determining its persistence through repeated testing.
Causes and Risk Factors
Common causes of proteinuria with normal eGFR include early diabetic nephropathy, hypertensive kidney disease, glomerulonephritis, or medication effects. In the case of the 28-year-old patient with IgAN, the degree of proteinuria was in the 'higher-risk' range, but GFR was normal 1. The Oxford Classification of IgAN has demonstrated the importance of mesangial hypercellularity, segmental glomerulosclerosis, endocapillary hypercellularity, and tubular atrophy/interstitial fibrosis as independent variables predicting kidney outcome 1.
Management
Management typically starts with blood pressure control using ACE inhibitors or ARBs, which specifically reduce proteinuria beyond their blood pressure-lowering effects 1. The guideline recommends long-term ACEi or ARB treatment when proteinuria is ≥1 g/day, with uptitration of the drug depending on BP 1. Lifestyle modifications are essential, including sodium restriction, moderate protein intake, regular exercise, and weight management.
Monitoring and Follow-up
Regular monitoring of kidney function and proteinuria every 3-6 months is necessary to assess response to treatment and disease progression 1. The patient was started on a low dose of an ACEi, which was gradually titrated up to a middle-range dose, and after 3 months of therapy, the urine protein levels fluctuated between 0.9 and 1.2 g/day 1. This approach is consistent with the guideline recommendation to titrate the ACEi or ARB upward as far as tolerated to achieve proteinuria ≤1 g/day 1.
Key Considerations
- Proteinuria reduction is associated with a more favorable prognosis, irrespective of whether the initial proteinuria was ≥3 g or of lesser degrees 1.
- BP control is crucial, with a target BP of ≤125/75 mm Hg in patients with proteinuria ≥1 g/day 1.
- Lifestyle modifications are essential to slow disease progression and reduce proteinuria 1.
From the FDA Drug Label
The RENAAL study was a randomized, placebo-controlled, double-blind, multicenter study conducted worldwide in 1513 patients with type 2 diabetes with nephropathy (defined as serum creatinine 1.3 to 3.0 mg/dL in females or males ≤60 kg and 1.5 to 3. 0 mg/dL in males >60 kg and proteinuria [urinary albumin to creatinine ratio ≥300 mg/g]) Compared with placebo, losartan significantly reduced proteinuria by an average of 34%, an effect that was evident within 3 months of starting therapy, and significantly reduced the rate of decline in glomerular filtration rate during the study by 13%, as measured by the reciprocal of the serum creatinine concentration
Normal eGFR but protein in the urine:
- The presence of protein in the urine (proteinuria) is a sign of kidney damage or disease.
- Losartan has been shown to reduce proteinuria by an average of 34% in patients with type 2 diabetes and nephropathy.
- However, the study does not directly address the scenario of a normal eGFR with protein in the urine.
- Key consideration: The use of losartan in patients with normal eGFR and proteinuria is not explicitly supported by the provided study, as the study focused on patients with type 2 diabetes and nephropathy.
- Clinical decision: In the absence of direct evidence, it is uncertain whether losartan would be beneficial for a patient with a normal eGFR and protein in the urine. 2
From the Research
Normal eGFR with Proteinuria
- Patients with normal eGFR and proteinuria in their urine may still be at risk of kidney disease progression 3
- The presence of proteinuria can indicate kidney damage, even if eGFR is normal 3
- Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can help reduce proteinuria in patients with chronic kidney disease (CKD), including those with normal eGFR 4, 5, 6
Treatment Options
- ACEIs and ARBs have been shown to be effective in reducing proteinuria in normotensive patients with CKD 4, 6
- Combination therapy of ACEIs and ARBs may be more effective in reducing proteinuria than monotherapy 4, 5
- The choice of treatment should be individualized based on the patient's specific condition and medical history 4, 7
Monitoring and Safety
- Patients with normal eGFR and proteinuria should be monitored regularly for changes in kidney function and proteinuria levels 3
- ACEIs and ARBs can cause hyperkalemia and changes in serum creatinine levels, which should be monitored closely 7
- The benefits of treatment should be weighed against the potential risks and side effects 7, 6