How to manage uncontrolled hypertension and elevated HbA1c with stable renal function but increased proteinuria?

From the Guidelines

Managing uncontrolled hypertension and elevated HbA1c with stable renal function but increased proteinuria requires initiating or maximizing an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) as first-line therapy, as recommended by the kdigo 2021 clinical practice guideline for the management of glomerular diseases 1. This approach not only helps in lowering blood pressure but also reduces proteinuria by decreasing intraglomerular pressure. For diabetes management, metformin remains the foundation therapy if not contraindicated by renal function, with a starting dose of 500 mg twice daily, increasing to 1000 mg twice daily as tolerated. Adding a sodium-glucose cotransporter-2 (SGLT2) inhibitor such as empagliflozin or dapagliflozin provides dual benefits of improving glycemic control while offering renal and cardiovascular protection. Key lifestyle modifications include:

• Sodium restriction to less than 2.0 g/day, as suggested by the kdigo 2021 guideline 1 and further emphasized by the importance of lifestyle changes in managing hypertension and proteinuria 1
• Regular physical activity
• Weight management
• Limiting alcohol consumption
• Stopping smoking, as highlighted in the 2007 guidelines for the management of arterial hypertension 1 Blood pressure should be monitored regularly with a target of <130/80 mmHg, while HbA1c should aim for <7% in most patients, in line with recommendations for managing hypertension in patients with diabetes 1. Regular monitoring of renal function, electrolytes, and proteinuria every 3-6 months is crucial to assess treatment efficacy and adjust medications accordingly, considering the goals of antihypertensive therapy in persons with reduced kidney function and/or diabetes 1. If blood pressure remains uncontrolled, adding a calcium channel blocker or a thiazide-like diuretic is recommended, as part of a multi-faceted approach to achieve blood pressure control and reduce proteinuria, aligning with the principles outlined in the prevention of hypertension and its complications 1.

From the FDA Drug Label

Losartan is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension In this population, losartan reduces the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end stage renal disease (need for dialysis or renal transplantation) The RENAAL study was a randomized, placebo-controlled, double-blind, multicenter study conducted worldwide in 1513 patients with type 2 diabetes with nephropathy Treatment with losartan resulted in a 16% risk reduction in the primary endpoint of doubling of serum creatinine, end-stage renal disease, or death Losartan also reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% as separate endpoints

The patient has uncontrolled hypertension and elevated HbA1c with stable renal function but increased proteinuria. Losartan can be considered to help manage the patient's condition, as it has been shown to reduce the rate of progression of nephropathy and proteinuria in patients with type 2 diabetes and a history of hypertension 2. Additionally, losartan can help lower blood pressure, which is also beneficial for the patient.

• Combining medications may be necessary to achieve blood pressure goals, and increasing metformin may help improve glycemic control.
• Amlodipine can also be considered to help manage hypertension, as it has been shown to reduce blood pressure and improve cardiovascular outcomes 3.
• However, the patient's increased proteinuria should be closely monitored, and the treatment plan should be adjusted accordingly.
• It is essential to weigh the benefits and risks of each medication and consider the patient's individual needs and medical history when making treatment decisions.

From the Research

Management of Uncontrolled Hypertension and Elevated HbA1c

• The patient's condition involves uncontrolled hypertension and elevated HbA1c, with stable renal function but increased proteinuria 4.
• The primary goal is to control blood pressure and reduce proteinuria, as hypertension is a risk factor for the progression of renal damage 4.
• International guidelines recommend lowering blood pressure to 140/90 mm Hg or less in patients with uncomplicated hypertension, and to 130/80 mm Hg or less for patients with diabetic or chronic renal disease 4.

Antihypertensive Therapy

• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) have beneficial effects on proteinuria and declining renal function, and are recommended as a first-line antihypertensive approach in patients with chronic kidney disease 4, 5.
• The addition of diuretics and calcium channel antagonists to RAS inhibitor therapy is also considered a rational strategy to reduce blood pressure and preserve renal function 4.
• Manidipine, a third-generation dihydropyridine calcium channel antagonist, has been shown to have beneficial effects on intrarenal haemodynamics, proteinuria, and other measures of renal functional decline in patients with chronic renal failure 4.

Lifestyle Interventions

• Sodium restriction is a valuable but often neglected antihypertensive strategy, and can lower blood pressure and enhance the anti-proteinuric effects of drugs that block the renin-angiotensin system 6.
• Educating the patient on how to interpret food labels and providing feedback by assessing sodium intake with 24-hour urine collection are effective sodium restriction strategies 6.

Monitoring and Follow-up

• Ambulatory blood pressure monitoring (ABPM) is mandatory to classify patients into true resistant hypertension (uncontrolled ambulatory BPs) and white-coat resistant hypertension (controlled ambulatory BPs), and to define the initial therapeutic approach 7.
• The treatment follow-up should be based on ABPM measurements, with the objective of achieving ambulatory blood pressure control 7.