What is the significance of impaired renal function, with a Blood Urea Nitrogen (BUN) level of 16, creatinine level of 1.24, and Glomerular Filtration Rate (GFR) of 48, in a patient with Diabetes Mellitus type 2 (DM2) and Hypertension (HTN)?

From the Guidelines

The patient's management should focus on slowing CKD progression through tight blood pressure control targeting <130/80 mmHg, preferably with an ACE inhibitor or an ARB, and diabetes management with metformin and an SGLT2 inhibitor, such as empagliflozin or dapagliflozin, as recommended by the most recent guidelines 1. The patient's lab values indicate Stage 3a chronic kidney disease (CKD) with a GFR of 48 mL/min/1.73m², mild elevation in creatinine (1.24 mg/dL), and normal BUN (16 mg/dL), complicated by diabetes type 2 and hypertension.

Key Management Strategies

• Tight blood pressure control targeting <130/80 mmHg, preferably with an ACE inhibitor like lisinopril 10-20 mg daily or an ARB such as losartan 50-100 mg daily, as these medications provide renoprotection by reducing intraglomerular pressure and proteinuria 1.
• Diabetes management with metformin, which can be continued at reduced doses (maximum 1000 mg daily) with careful monitoring, and an SGLT2 inhibitor, which has been shown to offer substantial benefits in reducing risks for CKD and CVD 1.
• Consideration of GLP-1 receptor agonists for additional glucose control and potential renal benefits.

Lifestyle Modifications

• Sodium restriction to less than 2 g/day to reduce blood pressure and slow CKD progression 1.
• Moderate protein intake of 0.8 g/kg/day to reduce the strain on the kidneys 1.
• Smoking cessation to reduce cardiovascular risk and slow CKD progression.
• Regular exercise, aiming for at least 150 minutes of moderate-intensity physical activity per week, to improve overall health and well-being 1.

Monitoring and Referral

• Regular monitoring with comprehensive metabolic panels every 3-6 months.
• Annual urine albumin-to-creatinine ratio testing to assess kidney damage and guide therapy.
• Medication dose adjustments based on GFR changes to optimize renal protection.
• Nephrology referral for specialized care planning and management of CKD complications.

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 the primary endpoint of doubling of serum creatinine, end-stage renal disease (ESRD) (need for dialysis or transplantation), or death. Treatment with losartan also reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% as separate endpoints, but had no effect on overall mortality.

Losartan Use in Patients with DM2 and HTN

• The patient's BUN 16, creatinine 1.24, and GFR 48 indicate impaired renal function.
• The RENAAL study suggests that losartan may be beneficial in reducing the risk of doubling of serum creatinine, ESRD, and death in patients with type 2 diabetes and nephropathy.
• However, the patient's GFR 48 is within the range of the study population, and the study results may be applicable to this patient.
• Monitoring of renal function and electrolytes is recommended when using losartan, especially in patients with impaired renal function 2.
• Avoid combined use of RAS inhibitors, such as ACE inhibitors or aliskiren, with losartan in patients with diabetes or renal impairment (GFR <60 mL/min) 2.

From the Research

Patient Profile

• BUN: 16
• Creatinine: 1.24
• GFR: 48
• Conditions: DM2 and HTN

Relevant Studies

• A study published in 2018 3 found that metformin may have an adverse effect on renal function in patients with type 2 DM and moderate CKD.
• Another study from 2018 4 discussed the importance of achieving and maintaining tight glycemic control in patients with T2DM and CKD, and highlighted the need for careful evaluation of contraindications and dosing adjustments for T2DM treatments in patients with renal impairment.
• A review from 2002 5 noted that while ACE inhibitors are frequently used to slow progression of nephropathy in patients with type 2 diabetes, evidence of their efficacy is limited and primarily drawn from small trials with surrogate end points.
• A 2016 review 6 discussed the role of the kidneys in T2DM and the therapeutic implications of SGLT2 inhibitors, which have been shown to have positive effects on measures such as glucose control, estimated glomerular filtration rate, and blood pressure in patients with T2DM.

Treatment Considerations

• Metformin may need to be used with caution or avoided in patients with moderate CKD 3.
• SGLT2 inhibitors may be contraindicated in patients with eGFR <45 mL/min/1.73m2 4.
• ACE inhibitors may be used to slow progression of nephropathy in patients with type 2 diabetes, but evidence of their efficacy is limited 5.
• SGLT2 inhibitors may represent an important extension to the diabetes treatment armamentarium, with potential benefits for renal and cardiovascular outcomes 6.