What is the workup for proteinuria in a 70-year-old male with a past medical history (PMHx) of diabetes mellitus (DM) and hypertension (HTN) with normal renal function?

From the Guidelines

For a 70-year-old male with diabetes, hypertension, and proteinuria, but normal kidney function, I strongly recommend initiating a renin-angiotensin-aldosterone system (RAAS) blocker, such as an ACE inhibitor or an ARB, to reduce proteinuria and slow potential kidney disease progression, as supported by the 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases 1.

Initial Workup and Management

The initial step should involve quantifying the proteinuria using a spot urine protein-to-creatinine ratio or a 24-hour urine collection to confirm the presence and extent of proteinuria.

• If proteinuria is confirmed (>300 mg/day), an ACE inhibitor such as lisinopril 10 mg daily or an ARB like losartan 50 mg daily should be initiated, titrating up as needed while closely monitoring blood pressure and kidney function.
• The target blood pressure should be less than 130/80 mmHg, as recommended for patients with hypertension and diabetes 1.
• Diabetes management should be optimized with a goal HbA1c of less than 7% to decrease microvascular complications, including diabetic nephropathy 1.

Ongoing Monitoring and Lifestyle Modifications

Regular monitoring should include:

• Quarterly urine protein assessments
• Serum creatinine
• Electrolytes, especially potassium, due to the potential effects of RAAS blockers on electrolyte balance Consider referral to a nephrologist if proteinuria exceeds 1 g/day or if there's a decline in kidney function. Lifestyle modifications are crucial and should include:
• Sodium restriction to less than 2g/day
• Moderate protein intake of about 0.8g/kg/day
• Regular exercise, aiming for at least 30 minutes, 5 times a week These modifications complement pharmacological therapy by further reducing proteinuria and alleviating CKD progression, as suggested by the evaluation and management of chronic kidney disease guidelines 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

The patient has a history of diabetes and hypertension with normal kidney function.

• Losartan may help reduce proteinuria in patients with diabetic nephropathy.
• The RENAAL study showed that losartan reduced proteinuria by an average of 34%.
• However, the patient's kidney function is normal, and the RENAAL study was conducted in patients with nephropathy and elevated serum creatinine.
• Therefore, the effectiveness of losartan in reducing proteinuria in this patient is uncertain, and the decision to use losartan should be based on individual patient factors and clinical judgment 2.

From the Research

Workup for Proteinuria in a 70-year-old Male with Diabetes and Hypertension

• The patient's proteinuria, diabetes, and hypertension require a comprehensive workup to determine the underlying cause and appropriate treatment 3, 4, 5, 6, 7
• The degree of proteinuria correlates strongly with the progression of nephropathy and cardiovascular events in patients with diabetes 3
• Reducing blood pressure and proteinuria can slow the progression of nephropathy 3

Treatment Options

• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) can reduce proteinuria and slow the progression of nephropathy 3, 4, 5, 7
• The combination of an ACE inhibitor and a non-dihydropyridine calcium antagonist can produce a greater reduction in proteinuria than either agent alone 3
• ARBs may be preferred over ACE inhibitors due to their improved safety profile and renoprotective effects 4, 7

Renal and Mortality Outcomes

• ACE inhibitors and ARBs can reduce the risk of end-stage renal disease and slow the progression of nephropathy, but may not decrease all-cause or cardiovascular mortality in patients with diabetes and proteinuria 5, 7
• The use of ACE inhibitors or ARBs can reduce the risk of doubling serum creatinine and progression of proteinuria, but may not improve regression of proteinuria 5

Additional Considerations

• Sodium-glucose cotransporter-2 (SGLT2) inhibitors may have competing effects with ACE inhibitors and ARBs on erythropoietin secretion and hematocrit values, which can have important clinical implications 6
• The relative contribution of each system to erythropoiesis and outcome remains to be revealed in future studies 6