Renal dysfunction is common in patients with heart failure and is associated with high morbidity and mortality. Cardiac and renal dysfunction may worsen each other through multiple mechanisms such as fluid overload and increased venous pressure, hypo-perfusion, neurohormonal and inflammatory activation, and concomitant treatment.
Full Answer
Do drugs used to treat heart failure affect renal function?
Further, the finding that biomarkers associated with renal tubular injury, as opposed to decreased filtration, are elevated in the setting of chronic and acute decompensated heart failure suggests “true” renal injury with heart failure and, that, optimization of cardiac function may not always be enough to restore renal function back to normal or reverse the damage that has occurred.
Does heart failure worsen renal function?
· A number of studies have demonstrated a linkage between renal dysfunction and adverse clinical outcomes in both acute and chronic heart failure. 1 – 3 Heart failure treatments can affect renal function in a variety of ways, with decreased glomerular filtration rate (GFR) during treatment often denoting a poorer prognosis. 4 – 6 Angiotensin-converting enzyme …
Is there a role for pharmacologic therapy in renal failure?
· Heart and kidney are closely related in the clinical syndrome of heart failure (HF). It is now sufficiently clear that renal dysfunction occurs frequently in all phenotypes of HF, and when present, it is associated with higher mortality and morbidity. While the pathophysiology is multifactorial, the most important factors are a reduced renal perfusion and venous congestion.
What is kidney disease in heart failure?
There is mounting evidence that chronic kidney disease itself is a major contributor to severe cardiac damage and, conversely, that congestive heart failure is a major cause of progressive chronic kidney disease. Uncontrolled congestive heart failure is often associated with a rapid fall in renal function and adequate control of congestive heart failure can prevent this.
What are the determinants of GFR in HF?
It must be emphasized again that, the main determinants of GFR in HF are renal haemodynamics and non-haemodynamic factors directly only account for a fraction of the pathophysiology. Having said that, these so-called cardiorenal connectors can shift the balance of susceptibility, severity, and mortality risk.6Also, the mechanisms by which these non-renal factors influence GFR are primarily through haemodynamic changes, and therefore, these factors are more mediators than direct effectors. A multitude of factors influence the association between haemodynamics and GFR. Of particular interest are (modulation of) the RAAS, sympathetic nervous system (SNS) activation, inflammation, endothelial dysfunction, and anaemia. Next to the direct effect on renal perfusion, angiotensin II promotes renal fibrosis, directly affects GFR, induces hyporesponsiveness to natriuretic peptide and mediates SNS activation.36–40The latter in turn can alter the ultrafiltration coefficient, and SNS activation is associated with tubular injury and the formation of reactive oxygen species (as well as RAAS activation).6,36,40The effect of oxidative stress and endothelial dysfunction seems to be modulated by angiotensin II as well. Through NADP(H) activation, angiotensin II promotes the formation of reactive oxygen species, which can cause intrarenal (proximal tubular) damage.6Finally, anaemia is an important factor in HF patients with renal impairment. Anaemia has diverse causes in HF, including reduced renal function with lower erythropoietin production and blunted response, bone marrow suppression in HF, iron deficiency, and not unimportantly, haemodilution due to excessive venous congestion which in some series is the most prevalent cause.41In acute HF, improvement of haemodiluted anaemia assessed by haemoconcentration does relate to better outcome and could even potentially be a target for therapy in these patients.17
What is the relationship between the heart and the kidneys?
The marriage between heart and kidney is like any other relationship ; it resembles a rollercoaster ride with frequent ups and downs, and in some cases, an unexpected early ending. In health, they both contribute to the wellbeing of the whole body. However, once either falls ill, the other organ frequently suffers as well. Although the heart has intense relationships with other organs, the marriage to the kidneys is particularly special. The heart is directly dependent of the regulation of salt and water content of the body by the kidneys, and vise versa, the kidneys are directly dependent of blood flow and pressure generated by the heart. This is especially true in conditions of increased congestion and extracellular water content, such as heart failure (HF), this interdependency of both organs can result in a vicious circle where deterioration of either organ results in a severe, potentially self-perpetuating, high-mortality condition. We have come to know this relationship as the cardiorenal syndrome, a term highlighting the fact that it represents a multitude of often overlapping disease states that all together are part of the same condition.1The last decade has seen a remarkable re-appraisal of the interaction between heart and kidney disease, especially in HF, and progress has been made in the recognition, risk stratification, and public awareness of the syndrome. Unfortunately, as we will discuss, there is no specific evidence-based effective treatment of patients with HF experiencing deterioration of renal function, although currently available HF treatment is not always insufficient. In the present review, we will highlight insights from the last 5 to 10 years in the terminology, pathophysiology, prognosis, and possible treatment of HF patients with concomitant renal dysfunction.
Is renal dysfunction a heterogeneous disorder?
Since renal dysfunction in patients with HF is a mechanistically heterogeneous disorder, it is logical to assume that prognosis and treatment may also differ. Unfortunately, phenotyping patients with renal dysfunction has proved a challenging endeavour since no gold standard exists by which HF-induced renal dysfunction can be differentiated from intrinsic renal parenchymal disease. However, it has been described that the majority of risk associated with renal dysfunction is restricted to patients with either an elevated NT-proBNP or an elevated BUN to creatinine ratio (BUN/Creat), markers which may help to identify HF-induced renal dysfunction.53,54Combination of these markers produces even more striking results.55Notably, patients with a low eGFR in the setting of an elevated BNP and BUN/Creat have multiple parameters consistent with HF-induced renal dysfunction including very poor prognosis but those patients with a low eGFR but normal BNP and BUN/Creat have a cardiorenal clinical profile and prognosis similar to patients without renal dysfunction. However, in the absence of a gold standard, it is impossible to determine if these markers are actually identifying mechanistically distinct types of renal dysfunction. Additional research within this domain is warranted.
Does HF affect renal function?
Impaired renal function in HF represents much more than simply a reduction in GFR. Albuminuria is frequently observed in patients with chronic HF as was observed in retrospective analyses of CHARM and GISSI-HF.42,43Around 30% of patients have albuminuria, many of which have microalbuminuria. When present there is a stepwise increase in the risk of HF hospitalizations and mortality from normo-, to micro- and macro-albuminuria. In addition to increased glomerular permeability, decreased re-absorption in the tubules due to tubular damage likely further contributes to the development of albuminuria. Tubular damage is now increasingly recognized in patients with acute and chronic HF.44,45Probably because of the fact that the kidney is one of the few organs that will simultaneously decrease oxygen delivery (reduced renal blood flow) while increasing relative oxygen requirement (since sodium reabsorption is highly energetically demanding), tubular damage may develop. In addition, increased congestion may be associated with tubular damage. In a retrospective analysis of GISSI-HF, tubular damage assessed by urinary markers such as N-acetyl-β-d-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (KIM-1) was frequently present among patients with chronic HF and strongly associated with mortality.44In acute HF, multiple studies have assessed the prevalence of tubular injury. Most of the research focusing on tubular damage markers in acute HF has been focused on the identification of patients at risk of WRF. In non-HF patient populations, tubular damage markers are sensitive and specific markers of severe AKI.46Unfortunately, studies in acute HF that have been conducted thus far have failed to demonstrate clinical usefulness of NGAL to identify patients at risk of clinical significant WRF, and notably in patients that do develop WRF urine NGAL levels do not meaningfully increase.47,48In chronic HF, urinary KIM-1 levels were the best predictors of WRF.49With respect to therapy, loop diuretics that seem to reduce urinary NAG and KIM-1 levels in stable HF patients and reducing congestion has been shown to improve albuminuria in acute HF.50,51Until we have more information on the clinical applicability of these novel (tubular) markers, their routine use in patients with HF does not seem justified yet.
Is RBF a determinant of GFR?
More importantly, the overall assumption in most contemporary studies has shifted from a RBF to a more CVP or venous congestion dependent explanation for GFR. However, this fails to acknowledge the fact that RBF remains—by far—the most important determinant of GFR in HF. GFR and RBF are by definition inexorably linked and under almost all circumstances, the RBF will be the primary driver of GFR. This relationship exists as GFR is simply the product of renal plasma flow times the filtration fraction. As a result, by definition renal plasma flow is an important determinant of GFR. Although there is a modest dynamic range of filtration fraction, a high value for filtration fraction multiplied by a very low RBF will still result in a low GFR, as is true of the opposite analogy. The relative contribution of venous congestion in these circumstances is marginal at best, and mostly seen in patients with compromised RBF. In acute HF, the importance of venous congestion in determining GFR is probably much greater, but we do not have data on RBF, venous congestion, and GFR in patients with acute HF. The relative contributions of these components are therefore unknown. Figure 3summarizes the pathophysiologic pathways of cardiorenal interaction.
Can creatinine increase with HF?
For chronic HF, the overall advice is similar. A small increase in serum creatinine is probably acceptable when the clinical status is stable or improves. There is however a special circumstance: the rise in serum creatinine that occurs in the setting of the initiation and uptitration of renin angiotensin aldosterone system (RAAS) inhibitors.20Several retrospective analyses of large randomized controlled RAAS-inhibitor trials have now re-evaluated these compounds in the light of the findings on WRF in the general HF population.21–24Most, if not all of these analyses have shown that if WRF occurs with the initiation of these therapies (including ACE-inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists), the beneficial effect of these therapies is maintained, and in some cases, this RAAS inhibitor induced WRF is not even associated with poor outcome. This is probably the net results of the strong protective effects of these agents balanced by the negative effects of WRF, or that these haemodynamic changes in filtration simply are not important. Importantly, the deterioration in eGFR in most of these studies was modest and thus these data provide limited evidence to indicate that it is safe (or unsafe) to continue these therapies if creatinine rises extensively. However, these data do clearly show that the beneficial effects of the treatment are maintained even in the setting of a modest rise in creatinine and thus some increase should be accepted with the caveat that frequent assessment of renal function and potassium should occur and are incorporated into good clinical judgment, as also indicated in the most recent ESC HF guidelines.20
Is a reduction in GFR a prognostic factor?
The prognostic importance of a reduction in GFR has only relatively recently been recognized. Two landmark retrospective analyses from randomized controlled trials showed that any reduction in eGFR was strongly associated with higher mortality rates.9,10Since then, over 50 studies have been published on the association between renal dysfunction and mortality.8Overall, the risk associated with concomitant renal dysfunction is around twice that of patients without evidence of renal dysfunction; an association that was independent of chronicity or phenotype of HF (Table 1).
What causes congestive heart failure?
The most common cause of congestive heart failure is ischemic heart disease. The prevalence of congestive heart failure increases greatly as the patient's renal function deteriorates, and, at end-stage renal disease, can reach 65-70%.
Can congestive heart failure cause anemia?
Anemia has been found in one-third to half the cases of congestive heart failure, and may be caused not only by chronic kidney disease but by the congestive heart failure itself. The anemia is associated with worsening cardiac and renal status and often with signs of malnutrition.
Is congestive heart failure a vicious circle?
Congestive heart failure, chronic kidney disease and anemia therefore appear to act together in a vicious circle in which each condition causes or exacerbates the other. Both congestive heart failure and anemia are often undertreated. Cooperation between nephrologists and other physicians in the treatment of patients with anemic congestive heart ...
Does congestive heart failure slow the progression of kidney disease?
Adequate and early det ection and aggressive treatment of congestive heart failure and chronic kidney disease and the associated anemia may markedly slow the progression of both diseases.
Does carvedilol help with congestive heart failure?
There is new evidence showing the cardioprotective effect of carvedilol in patients on dialysis, and of simvastatin and eplerenone in patients with congestive heart failure. Use of non-steroidal anti-inflammatory drugs doubles the rate ...
How to treat kidney disease?
Another important part of treating kidney disease and heart disease includes living a healthy lifestyle . Staying active can help protect your kidneys and your heart. Try to be active for 30 minutes or more most days of the week. Start with easy activities such as walking slowly or raking leaves. Later, try some activities that get your heart pumping, such as walking briskly or swimming. Always talk with your health care provider before starting any new exercise program. You can find more information about about weight control and physical activity at NIDDK's Weight Control Information Network. See the “ Eating, Diet, and Nutrition ” section below for tips on eating a healthy diet that will protect your heart and kidneys.
What is the most common cause of death for people with kidney disease?
Heart disease is the most common cause of death among people who have kidney disease. Kidney disease means that the kidneys are damaged and can’t filter blood as they should. This damage can cause wastes to build up in the body.
What is the term for the loss of kidney function?
For most people, kidney damage occurs slowly over many years. This gradual loss of kidney function is called chronic kidney disease (CKD). Most patients with CKD have no symptoms until kidney damage is advanced.
How to lower your chance of kidney disease?
However, you can lower your chance of having kidney disease and heart disease by taking the following steps: See your health care provider as directed. Keep your blood pressure below 140/90. Follow your provider’s advice on how to stay at or below your target. Control your blood glucose if you have diabetes.
What is the most common disease that you will get if you have kidney disease?
If you have kidney disease, you are more likely to get heart disease .
Can you control blood glucose with kidney disease?
If you have kidney disease or heart disease, your health care provider will want you to control your blood glucose if you have diabetes and your blood pressure if you have high blood pressure. Your health care provider may prescribe medicines to keep your blood glucose and blood pressure under control.
What is the test for heart disease?
Another test, called a stress test, measures how your heart works during physical activity, such as walking, running on a treadmill, or riding a bike. This test usually takes place in a hospital or a specialized outpatient center. If these tests show that you have heart disease, your doctor may want to do more tests.
What are the diseases that affect the heart and kidneys?
Several medical problems that can affect multiple organ systems, such as diabetes or lupus, often produce disease of both the heart and kidneys.
How to avoid kidney disease?
If you have a cardiac diagnosis, the best way to avoid developing kidney disease is to make sure you are receiving all the appropriate therapy for your heart condition. This means not only getting all the treatment you need for the underlying heart condition itself (whether it’s CAD, heart valve disease, cardiomyopathy, or any other condition) but also doing everything you can to achieve and maintain the optimal health of your cardiovascular system in general. This means aggressively treating hypertension, diabetes, and elevated lipids, maintaining a healthy weight, not smoking, and getting plenty of exercise.
What is the relationship between heart and kidney?
So, if either the heart or the kidneys are affected by some form of the disease, there is a relatively high risk that the other organ will also develop medical problems. This general relationship between heart and kidney disease has sometimes been called the cardiorenal syndrome .
Why do toxins accumulate in the blood?
For instance, the toxins that accumulate in the blood because of abnormal kidney function (the so-called uremic toxins) increase the risk for CAD. Other blood and metabolic abnormalities associated with chronic kidney disease also increase the risk.
Why do people with kidney disease have a high risk of developing CAD?
These include smoking, diabetes, high cholesterol , hypertension, sedentary lifestyle, and older age.
What changes occur in the sympathetic nervous system during heart failure?
Neurohumoral changes. To compensate for the drop in cardiac output that often occurs in heart failure, a number of changes occur in the sympathetic nervous system and in the hormones that control the volume of salt and water in the circulation—that is, in the renin-angiotensin-aldosterone system.
What happens when you have a drop in cardiac output?
This decrease in blood flow can reduce the volume of blood being filtered by the kidneys, which causes renal function to deteriorate.
What are the consequences of a decline in renal function in a patient with heart failure?
The consequences of a decline in renal function in a patient with heart failure depend on the clinical setting. 39 Patients with hypotension or shock behave differently from those with progressive symptoms but who are euvolaemic and differently again from those with fluid retention (decompensation with congestion) as discussed here.
Why does creatinine rise in heart failure?
Because patients with heart failure commonly have reduced renal function , even a small decline in renal function may produce a rise in creatinine large enough to trigger an e-alert and the stopping of prognostically vital medication. An ‘AKI’ alert in a patient starting RAAS inhibitors in a patient with HFrEF does not mean the RAAS inhibitor should be stopped but should stimulate a careful search for potentially reversible causes of renal decline.
What causes a decrease in GFR?
Increased activity of the RAAS causes glomerular arteriolar vasoconstriction that is more marked in the efferent than the afferent arteriole, helping to preserve GFR. Non-osmotic anti-diuretic hormone (ADH) release contributes to hyponatraemia and also to increased urea reabsorption in the collecting duct: a disproportionate rise in blood urea is a marker of poor prognosis in patients with acute decompensated heart failure. 17 Other neurohormones, particularly natriuretic peptides, counteract the effects of RAAS activation. GFR is also dependent on the vasodilator effects of prostaglandins. Non-steroidal anti-inflammatory drugs can therefore cause a marked fall in GFR.
Why should diuretics be titrated?
Diuretics should be titrated to prevent distress from fluid overload, irrespective of renal function. If there is symptomatic hypotension, discontinuation of RAAS blockade is appropriate. Higher doses of diuretics than are commonly used are needed to treat congestion in the fluid overloaded patient.
What is the treatment for CHF?
Treatment with ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), sacubitril/valsartan, beta-blockers and mineralocorticoid receptor antagonists (MRAs) (together with appropriate device therapy) increase life expectancy markedly, with the combination of sacubitril/valsartan, beta-blocker and MRA reducing all-cause mortality with a HR of 0.37 against placebo. 1 However, there is frequently a conflict between renal function and heart failure therapy. Renal dysfunction is extremely common in patients with CHF ( figure 1) and associated with a worse outcome. 2 Most of the treatments used for CHF can cause worsening renal function.
Does RAAS inhibitor help with heart failure?
RAAS inhibition has no known prognostic benefit in heart failure with preserved ejection fraction. Efforts should be made to initiate, titrate and maintain patients with HFrEF on RAAS inhibitor treatment, whether during intercurrent illness or worsening heart failure. heart failure with reduced ejection fraction.
Is AKI associated with worsening renal function?
CKD and AKI are undoubtedly associated with a poor prognosis in patients with HF, 40 but it is far from clear that worsening renal function drives the association. Worsening renal function is only associated with a worse prognosis in patients whose signs of congestion persist at discharge. 41 42 It feels intuitively obvious that an improvement in eGFR must be related to better outcome, but improving renal function is, in fact, associated with worse outcome. 43 Figure 2 shows data from a post hoc analysis of the Diuretic Strategies in Patients with Acute Decompensated Heart Failure trial, 44 in which patients who were hospitalised with congestion were randomised to a high versus low dose intravenous diuretic regimen. Improvement in eGFR at 72 hours was independently associated with increased risk of the composite end point of death, hospitalisation for HF or visit to the emergency department. The association may reflect inadequate optimisation of fluid balance.
What happens when the kidneys are impaired?
When the kidneys become impaired, the hormone system, which regulates blood pressure, goes into overdrive in an attempt to increase blood supply to the kidneys. The heart then has to pump against higher pressure in the arteries, and eventually suffers from the increase in workload.
What is the role of the kidney in the body?
The heart’s job is to send a continuous supply of oxygenated blood around the body. The kidney filters the blood, extracting waste in the form of urine, and also helps regulate the water and salt levels to control blood pressure.
What is the best way to reduce blood pressure?
Water tablets, or diuretics, help reduce blood pressure and remove excess fluid as they make the kidneys excrete more water and salt. Swollen ankles are a common indication of excess fluid: talk to your doctor if this keeps happening to you.
What test can be done to check kidney function?
It’s routine for doctors to check your kidney function if they believe you may have heart disease. A simple blood test can check if the level of creatinine, a waste product usually secreted by the kidneys, is raised, suggesting impairment. Some patients may also need an ultrasound or CT scan to help examine their kidneys’ structure and function.
How to lower blood pressure?
Exercise regularly – swimming, cycling, dancing or power walking all help to lower blood pressure and improve heart and muscle function.
How to reduce the risk of a syringe?
How you can reduce your risk: 1 Be a non-smoker. 2 Eat a low-salt diet. 3 Ask your doctor or nurse how to adjust drug dosage according to your blood test results and weight. Weigh yourself regularly at home to warn of fluid overload or dehydration. 4 Get to know your drugs – ask your doctor, specialist nurse or pharmacist to explain. 5 Exercise regularly – swimming, cycling, dancing or power walking all help to lower blood pressure and improve heart and muscle function.
Can heart failure cause kidney problems?
Relatively recent research has shown that heart failure is a significant risk factor for kidney disease. When the heart is no longer pumping efficiently it becomes congested with blood, causing pressure to build up in the main vein connected to the kidneys and leading to congestion of blood in the kidneys, too.
What percentage of patients with heart failure have CKD?
Approximately 30%–60% of patients with heart failure reach criteria for having CKD (eGFR<60 ml/min per 1.73 m 2 ). In a systematic review of 80,000 hospitalized and nonhospitalized individuals with heart failure, 29% had kidney impairment ( 19 ), while in the Acute Decompensated Heart Failure National Registry (ADHERE) database, which has >100,000 individuals, approximately 30% had creatinine values >2 mg/dl ( 20 ). The broad ranges in prevalence of CKD are related to varying definitions, differences in the observed time at risk, and the heterogeneity of selected populations being studied. There is also a 20%–30% incidence of AKI during treatment for heart failure ( 21 – 24 ).
How many ml/min before kidney transplant?
There remains no standardized guidelines for when to perform simultaneous heart and kidney (SHK) transplants, even though as many as 30% of heart transplant recipients have an eGFR<45 ml/min per 1.73 m 2 before their transplant ( 58 ). Lower eGFR is a risk factor for death after heart transplant ( 59 ).
What were the findings of a pertinent physical examination?
Pertinent physical examination findings included BP, 130/74 mmHg; heart rate, 84 beats/min; respiratory rate, 18 breaths/min; and weight, 88.7 kg (increased >10 kg during the last few months). Jugular venous pressure was elevated to the angle of the jaw with the patient at 45 degrees. Heart rate was irregular, with a II/VI systolic murmur loudest at the left sternal border. There were bibasilar crackles, tense ascites, and 2+ pitting edema bilaterally up to the knees. He had an arteriovenous fistula in his left arm.
Can diuresis be done with heart failure?
No trial data support target rates of diuresis in patients with heart failure. From a pathophysiologic standpoint, diuresis should not significantly exceed interstitial fluid mobilization rate so as to avoid hypotension and further neurohormonal activation. In practice, it is reasonable to initially target a net negative balance of about 1 L per day, but this is highly variable and should be modified by the clinical urgency, hemodynamic stability, and kidney function response.
Is ultrafiltration better than diuretics?
In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD) study ( 44 ), 200 patients with heart failure were randomly assigned to ultrafiltration or diuretics. Ultrafiltration produced greater weight loss than diuretics and reduced 90-day resource utilization for heart failure. One critique of the trial was that the diuretic doses used were below what one would use in standard of care, although similar results were noted in the Relief for Acutely Fluid Overloaded Patients with Decompensated Congestive Heart Failure trial. The most recent study to evaluate this issue incorporated changes in diuretic doses and randomly assigned 188 patients with acute decompensated heart failure, as well as decline in kidney function and congestion, to stepped pharmacologic therapy or ultrafiltration (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). The primary outcome was a bivariate change in kidney function and body weight. Stepped pharmacologic therapy was superior to ultrafiltration for preservation of kidney function, despite similar weight loss ( 45 ). A critique of this trial was that the mechanism of implementation of ultrafiltration differed from that of the UNLOAD trial. Thus, the utility of ultrafiltration remains unresolved and additional trials are ongoing.
Is CKD a CRS?
CKD due to heart failure or the cardiorenal syndrome (CRS), therefore, was high on the differential diagnosis list. However, other diseases to consider would be renovascular disease, prior atheroembolic disease, tubulointerstitial disease, and myeloma kidney.
Is high central venous pressure a risk factor for death?
High central venous pressure (CVP) is a risk factor for death ( 3, 8) and has been associated with lower eGFR at baseline and decline in eGFR ( 3 ). For example, in a study of 145 patients with decompensated heart failure, kidney function declined less frequently when CVP was <8 cm ( 3 ), and the ability of CVP to stratify risk was independent of heart rate, pulmonary wedge pressure, systolic BP, cardiac index, and eGFR. Other studies, however, have not reproduced these findings ( 9, 10 ), and a recent editorial has highlighted the complexity of interpretation of epidemiologic studies evaluating the relationships between CVP and progression of kidney disease ( 11 ).
