What is the most likely diagnosis 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

The most likely diagnosis for proteinuria in a 70-year-old male with diabetes and hypertension but normal kidney function is diabetic nephropathy.

Initial Workup

The initial workup should include:

• Quantification of proteinuria with a spot urine protein-to-creatinine ratio or a 24-hour urine collection
• A complete metabolic panel
• Urinalysis
• Hemoglobin A1c Additional testing should include a renal ultrasound to assess kidney structure and rule out obstruction. Diabetic nephropathy typically presents with gradually increasing proteinuria, often beginning with microalbuminuria (30-300 mg/day) before progressing to overt proteinuria (>300 mg/day) 1. Despite normal kidney function (normal GFR), early diabetic nephropathy can manifest solely as proteinuria.

Management

Management should focus on:

• Optimizing glycemic control (target HbA1c <7%)
• Blood pressure control (target <130/80 mmHg)
• Initiating an ACE inhibitor or ARB (such as lisinopril 10-40 mg daily or losartan 50-100 mg daily) which reduce proteinuria and slow disease progression 1. Regular monitoring of kidney function, proteinuria, and electrolytes is essential, particularly after starting RAAS blockade therapy. The use of ACEi or ARB has been associated with proteinuria reduction and a reduction in GFR decline in patients with proteinuria >1 g/day and, together with strict BP targets, should be instituted in all patients who are at higher risk for progression 1. Microalbuminuria can be measured from spot urine samples by indexing the urinary albumin concentration to the urinary creatinine concentration 1. Patients with microalbuminuria and proteinuria should be treated with an ACE inhibitor or angiotensin II receptor antagonist regardless of baseline BP 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]) Treatment with losartan resulted in a 16% risk reduction in this endpoint Compared with placebo, losartan significantly reduced proteinuria by an average of 34%, an effect that was evident within 3 months of starting therapy

The most likely diagnosis is Diabetic Nephropathy.

• Key points:
  • The patient has a history of diabetes and hypertension
  • The patient has normal kidney function but proteinuria
  • Losartan has been shown to reduce proteinuria and slow the progression of renal disease in patients with diabetic nephropathy 2
• Clinical decision: Diabetic nephropathy is a common complication of diabetes and can be diagnosed based on the presence of proteinuria and a history of diabetes. The use of losartan, an angiotensin II receptor antagonist, has been shown to be effective in reducing proteinuria and slowing the progression of renal disease in patients with diabetic nephropathy.

From the Research

Diagnosis of Proteinuria in a 70-Year-Old Male

Given the patient's past medical history (PMHx) of diabetes and hypertension (HTN) with normal kidney function, the diagnosis of proteinuria is likely related to one of these conditions.

• The patient's diabetes and hypertension increase the risk of developing diabetic nephropathy (DN) or hypertensive nephrosclerosis (HN) 3, 4, 5, 6.
• Diabetic nephropathy is a major complication of both type 1 and type 2 diabetes, characterized by an elevated urinary albumin excretion rate, increased blood pressure, and a continual loss of renal function 4, 5.
• Hypertensive nephrosclerosis is also a common cause of chronic kidney disease (CKD), and patients with HN have a more favorable outcome compared to those with DN 3.
• The study by 7 suggests that spot urine protein-creatinine ratio can be used as a faster diagnostic substitute for 24-hour urinary protein estimation, which can aid in the diagnosis of proteinuria.

Possible Causes of Proteinuria

Considering the patient's normal kidney function, the possible causes of proteinuria include:

• Diabetic nephropathy (DN) 4, 5
• Hypertensive nephrosclerosis (HN) 3, 6
• Other conditions such as kidney damage or disease, which may not be directly related to the patient's diabetes or hypertension.

Further Evaluation

To determine the underlying cause of proteinuria, further evaluation is necessary, including:

• Urine tests to measure protein levels and detect any abnormalities 7
• Blood tests to assess kidney function and detect any signs of kidney damage
• Imaging studies, such as ultrasound or CT scans, to visualize the kidneys and detect any abnormalities
• Kidney biopsy to distinguish between DN and HN, as suggested by 3