What Are The Treatment Strategies And Attention Issues For Heart Failure in Patients With CKD?
Apr 13, 2023
Heart failure with reduced ejection fraction (HFrEF) is a common comorbidity in CKD patients. About 50% of HFrEF patients have an estimated glomerular filtration rate (eGFR) <60ml/min/1.73㎡, and 20% of heart failure patients have eGFR<30ml/min/1.73㎡. In addition, patients with CKD and heart failure had a significantly worse prognosis than those without CKD. Notably, cardiovascular events are the leading cause of death in CKD patients. So, for patients with CKD and HFrEF, how to use drugs?
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In February 2023, Current Heart Failure Reports released a review from France, pointing out that for HFrEF patients with CKD, the available drugs include angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor II antagonist (ARB), angiotensin receptor neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonist (MRA), and sodium-glucose cotransporter 2 inhibitors (SGLT-2i). However, compared with patients with only HFrEF, the medication methods for patients with HFrEF combined with CKD are more complicated, and more CKD-specific adverse event risks need to be paid attention to.
Current status of drug use in patients with CKD complicated with heart failure
In clinical practice, renal function assessment usually uses eGFR. However, physicians need to be aware that eGFR has limitations, as it may be influenced by the individual patient's physiological state and medication use. For example, eGFR does not accurately reflect renal function in patients with abnormal muscle mass or on diuretics. In addition, drugs, diabetes, ACEi/ARB, non-steroidal anti-inflammatory drugs, etc. may also affect eGFR. However, the sites of the effect of these drugs vary. For example, ACEi/ARB and diuretics can affect renal perfusion in patients, thereby affecting eGFR; non-steroidal anti-inflammatory drugs may affect renal interstitium and renal tubules (Figure 1). In short, drugs commonly used to treat CKD and heart failure may affect kidney function. Physicians need to be familiar with the above influencing factors, and be alert to changes in renal function during the treatment of patients.
Figure 1 Factors Affecting GFR
Figure 2 shows the drug use in CKD patients with HFrEF at different eGFR levels. It is worth noting that many patients do not remain stable on their medications, but periodically stop or restart their medications. In addition, compared with patients with eGFR ≥ 60ml/min/1.73㎡, the medication situation of patients with eGFR<30ml/min/1.73㎡ is more complicated.
Figure 2 Drug use in CKD patients with HFrEF
Although the drug use of CKD patients with HFrEF is complicated, it mainly focuses on 5 drugs, namely ACEi/ARB, ARNI, MRA, β-blockers, and SGLT-2i.
5 major drug regimens
1 ACEi/ARB
Both ACEi/ARB can directly affect the hemodynamics in the glomerulus, thereby reducing the internal blood pressure and leading to a decrease in eGFR. However, in the long run, ACEi/ARB can help maintain the patient's eGFR and prevent the patient's glomeruli from being damaged due to high blood pressure. Therefore, the "kidney injury" caused by ACEi/ARB is transient, which reduces eGFR in the short term but is beneficial to the preservation of eGFR in patients in the long term.
Recent evidence suggests that, in clinical practice, ACEi/ARB should be continued for cardiovascular benefit in CKD patients with eGFR <30ml/min/1.73m2. Therefore, if no apparent renal injury is found in CKD patients with HFrEF, ACEi/ARB should be continued rather than discontinued due to low eGFR levels.
2 ARNI
ARNI is a new drug for the treatment of heart failure. In addition to treating heart failure, it can also increase the patient's GFR. In clinical practice, ARNI can significantly improve the risk of cardiovascular mortality and heart failure hospitalization in patients, regardless of whether patients have CKD or not. ARNI is also safe and effective for dialysis patients.
It is worth noting that ARNI can significantly lower blood pressure, which may lead to lower renal perfusion and permanent damage to the kidneys. In contrast to ACEi, this damage appears to be irreversible. Some post hoc analyzes showed that ARNI was significantly better than ACEI in terms of long-term eGFR preservation and reduction in the risk of renal events. However, these data analyses excluded patients with severe hypotension. This means that CKD patients with HFrEF should pay attention to their blood pressure and renal perfusion when receiving ARNI treatment to avoid severe hypotension and renal hypoperfusion.
3 MRA
MRA can prevent abnormal overactivation of mineralocorticoid receptors, thereby treating the heart and kidney-related inflammation and fibrosis. Existing evidence shows that MRA can safely and effectively treat HFrEF patients with CKD with eGFR<60ml/min/1.73㎡.
Meta-analysis showed that using MRA in dialysis patients can significantly reduce the risk of cardiovascular events. In addition, finerenone, a new non-steroidal selective MRA, can delay the progression of CKD and the risk of cardiovascular events, and its risk of hyperkalemia is low. This suggests that finerenone is safer and more effective than traditional MRA.
4 beta blockers
Beta-blockers are the only drugs that do not have a direct effect on renal hemodynamics. A meta-analysis that included 10 clinical studies showed that β-blockers can improve the cardiovascular outcomes of CKD patients, and are also effective for patients with eGFR between 30 and 44ml/min/1.73㎡. What's more, beta-blockers did not cause a worsening of kidney function. In conclusion, β-blockers can prevent and treat heart failure in patients with CKD without negatively affecting renal function.
5 SGLT-2i
Multiple studies have shown that SGLT-2i has a significant cardiorenal protective effect on CKD patients, including patients with eGFR ranging from 20 to 30ml/min/1.73㎡. Although some patients may experience a short-term decrease in eGFR after taking SGLT-2i for the first time, in the long run, SGLT-2i can significantly reduce the rate of eGFR decline, the risk of developing an end-stage renal disease, or death from renal causes.
Adverse event
Common adverse events in patients treated for CKD with HFrEF include worsening renal function, hyperkalemia, and hypotension. However, the risk of these adverse events and their harm to patients can be reduced by monitoring and adjusting prescriptions.
1 Kidney function deterioration
In patients with HFrEF, worsening renal function (increase in serum creatinine > 0.3 mg/dl) is a common phenomenon. Most drugs used to treat heart failures, such as ACEi/ARB, SGLT-2i, and ARNI, may reduce eGFR, but these changes are usually associated with hemodynamic changes in patients and do not imply substantial damage to the kidneys or glomeruli. Over the long term, kidney disease progressed more slowly in patients taking the drugs than in patients not. Therefore, these drugs for the treatment of heart failure should not be considered nephrotoxic drugs, but renal hemodynamic modulators. In the early stage of using the above drugs, if the patient's creatinine level rises sharply, a renal Doppler examination should be performed to evaluate the renal blood circulation and take timely intervention measures.
2 Hyperkalemia
Hyperkalemia is the main reason for discontinuation of ACEi/ARB or MRA in CKD patients, which is related to two important factors: ①The risk of death from hyperkalemia is higher; ②Compared with the general population, CKD patients are more prone to hyperkalemia Kalemia, while the use of ACEi/ARB or MRA will exacerbate this risk. However, the following four approaches can reduce a patient's risk of developing hyperkalemia.
①Adjust the drug dose according to renal function. For example, the dose of spironolactone should be as low as possible, and the frequency of medication should be adjusted to 2-3 times a week, while the blood potassium level should be monitored in real-time. The STRONGHF study showed that 80% of patients could use MRA by adjusting prescription + blood potassium monitoring.
② Active use of potassium binders, such as Patiromer, sodium zirconium cyclosilicate, and other drugs. The DIAMOND study showed that the Patiromer group had a lower risk of hyperkalemia compared with the placebo group (HR = 0.63; P = 0.006). In patients with advanced CKD (eGFR=15ml/min/1.73㎡) receiving ACEi/ARB therapy, the risk of hyperkalemia was significantly lower in the Patiromer group (60% vs 15%; P < 0.001).
③Use of SGLT-2i can significantly reduce the risk of hyperkalemia. In a large meta-study including 50,000 patients, SGLT-2i significantly reduced the risk of hyperkalemia by 16% compared with placebo, with no increase in the risk of hypokalemia. What's more, similar results were found in patients with heart failure.
④ Low potassium diet can also reduce the risk of hyperkalemia.
3 low blood pressure
Hypotension is common in patients with heart failure. However, hypotension in heart failure patients is caused by a variety of factors, including changes in systolic function, low volume, and drug effects. Therefore, when using the above drugs, it is necessary to carefully inquire about the patient's medical history and medication conditions, such as whether to take diuretics, and whether diarrhea or dehydration has occurred recently, to avoid the occurrence of hypotension. In addition, for patients with heart failure with a history of hypotension, the prescription should be adjusted carefully.
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Cistanche is a traditional Chinese herb that is commonly used in Chinese medicine to treat kidney disease. Scientific studies have shown that cistanche has several medicinal properties that make it effective in treating kidney disease.
Firstly, cistanche has immunomodulatory effects that can help strengthen the immune system, which is important in treating kidney disease as it commonly involves an inflammatory response.
Secondly, cistanche contains a group of natural compounds called phenylethanoid glycosides (PEGs) that have antioxidant and anti-inflammatory properties. These properties help to protect the kidneys against oxidative stress and inflammation, which are two of the main causes of kidney damage.
Lastly, cistanche has been shown to increase the production of cytokines and chemokines that promote cell growth and regeneration in the kidneys, which can help improve kidney function.
Overall, cistanche can be an effective treatment for kidney disease by reducing inflammation, protecting against oxidative stress, and promoting cell growth and regeneration in the kidneys.
References:
1. Enachi S, Schleef M, Hadjseyd CE, et al. Challenges and Opportunities in Titrating Disease-Modifying Therapies in Heart Failure with Reduced Ejection Fraction and Chronic Kidney Disease. Curr Heart Fail Rep. 2023 Feb 28.
