From the Guidelines
For a patient with Chronic Kidney Disease (CKD) and proteinuria, with impaired renal function, the most effective long-term treatment approach is to start with renin–angiotensin system inhibitors (RASI) therapy, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), as it reduces both cardiovascular event rates and kidney end points, as recommended by the 2021 KDIGO clinical practice guideline 1. When considering the management of blood pressure in patients with CKD, it's crucial to prioritize the reduction of proteinuria and the preservation of renal function. The use of RASI therapy is supported by evidence from several placebo-controlled RCTs, which have shown a clear reduction in the risks for both kidney failure and cardiovascular events, particularly in patients with severely increased albuminuria 1. Key considerations in the management of CKD include:
- The importance of achieving a systolic blood pressure (SBP) target of less than 120 mm Hg, as recommended by the 2021 KDIGO guideline 1
- The need for individualized treatment plans, taking into account the patient's specific disease characteristics, such as the presence of diabetes and the level of proteinuria
- The potential benefits and risks of intensive blood pressure control, including the risk of hyperkalemia, hypokalemia, and acute kidney injury 1 In terms of specific treatment recommendations, the 2021 KDIGO guideline suggests starting RASI therapy for people with high blood pressure, CKD, and severely increased albuminuria, without diabetes 1. It's also important to note that many patients with CKD will require combination therapy to achieve the desired blood pressure target, and that evidence-based recommendations are limited to the choice of initial therapy 1. Overall, the management of CKD requires a comprehensive and individualized approach, taking into account the latest evidence-based guidelines and the patient's unique disease characteristics.
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 (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.
The implications of long-term treatment for a patient with Chronic Kidney Disease (CKD) and Proteinuria, with Impaired Renal Function are:
- Reduced risk of doubling of serum creatinine by 25%
- Reduced risk of End-Stage Renal Disease (ESRD) by 29%
- Reduced risk of the primary composite endpoint (doubling of serum creatinine, ESRD, or death) by 16%
- No effect on overall mortality These effects were observed in the RENAAL study 2.
From the Research
Implications of Long-Term Treatment for CKD and Proteinuria
The implications of long-term treatment for a patient with Chronic Kidney Disease (CKD) and Proteinuria, with Impaired Renal Function, can be understood through various studies.
- The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) has been shown to reduce proteinuria in CKD patients 3.
- A study found that the combination therapy of olmesartan and temocapril had the highest probability of being the most effective treatment to reduce proteinuria in normotensive CKD patients 3.
- Another study suggested that triple blockade of the renin-angiotensin-aldosterone system with ACE-I, ARB, and mineralocorticoid receptor blocker (MRB) could be useful for CKD patients with massive proteinuria 4.
- The addition of hydrochlorothiazide to losartan has been shown to reduce proteinuria in CKD patients with hypertension 5.
Treatment Strategies
Different treatment strategies have been proposed for CKD patients with proteinuria, including:
- Monotherapy with ACEIs or ARBs 3
- Combination therapy with ACEIs and ARBs 3, 6
- Triple blockade of the renin-angiotensin-aldosterone system with ACE-I, ARB, and MRB 4
- Addition of diuretics such as hydrochlorothiazide to ACEIs or ARBs 5
Clinical Audit and Guidelines
A clinical audit found that proteinuria assessment and therapeutic management of CKD patients were not fully in line with KDIGO guidelines, and improvements are needed 7.