The mechanisms by which the onset of acute HF or acutely decompensated chronic HF leads to AKI are multiple and complex (4) (Fig. 1). The clinical importance of each mechanism is likely to vary from patient to patient (e.g., acute cardiogenic shock vs. hypertensive pulmonary edema) and situation to situation (acute HF secondary to perforation of a mitral valve leaflet from endocarditis vs. worsening right HF secondary to noncompliance with diuretic therapy).
1- Impaired renal perfusion 2- Diuretics hyporesponsivness and Diuretic Braking 3- ACEs and ARBs with or without hyperkalemia 4- Contrast nephropathy after angiography
Even slight decreases in estimated glomerular filtration rate (GFR) significantly increase mortality risk (54) and are considered a marker of severity of vascular disease. Independent predictors of worsening function include old age, hypertension, diabetes mellitus, and acute coronary syndromes.
Acute kidney injury can affect the heart through several pathways (Fig. 3), whose hierarchy is not yet established. 1- Fluid overload can contribute to the development of pulmonary edema. 2- Hyperkalemia can contribute to arrhythmias and may cause cardiac arrest. 3- Untreated uremia affects myocardial contractility through the accumulation of myocardial depressant factors (66) and pericarditis (67). 4- Acidemia produces pulmonary vasoconstriction (68), which can significantly contribute to right-sided HF. Acidemia appears to have a negative inotropic effect (69) and might, together with electrolyte imbalances, contribute to an increased risk of arrhythmias (70). 5- renal ischemia itself may precipitate activation of inflammation and apoptosis at cardiac level
A unique situation leading to type 3 CRS is bilateral renal artery stenosis Patients with this condition may be prone to acute or decompensated HF because of diastolic dysfunction related to chronic increase of blood pressure from excessive activation of the renin-angiotensin-aldosterone axis, renal dysfunction with sodium and water retention, and acute myocardial ischemia from an increase in myocardial oxygen demand related to intense peripheral vasoconstriction (71,72). In these patients, angiotensin blockade is generally required to manage the hypertension and HF. However, the GFR is highly dependent upon angiotensin and significant decompensation of kidney function may ensue. Although the management of these unusual patients has not been subject to scrutiny in large randomized trials, those exhibiting renal decompensation with ACE inhibition or ARB are likely candidates for renal revascularization
Many medications necessary for management of complications of advanced CKD generally are considered safe with concomitant cardiac disease. These include regimens for calcium-phosphate balance and hyperparathyroidism, vitamins, and erythropoiesis-stimulating agents. The same appears to hold true for novel regimens, for instance, endothelin system antagonists, adenosine and vasopressin receptor antagonists, and inflammation suppressors. For immunosuppressive drugs, controversy exists regarding the effects of certain agents on the heart, indicating a need for more research in the area. Other medications requiring thorough considerations of pros and cons include diuretics, digitalis, calcium-channel blockers, and nesiritide
Dr. Anass Qasem
Cardiac diseases are associated independentlywith a decrease in kidney function and progression ofexisting kidney diseases. Conversely, chronic kidneydisease (CKD) represents an independent risk factorfor cardiovascular events and outcomes.
In patients with acute decompensated heartfailure (ADHF), an acute increase in serum creatininelevel > 0.3 mg/dl is associated with increasedmortality, longer hospital stays, and more frequentreadmissions.
An acute increase in serum creatinine levelaccompanies 21%-45% of hospitalizations for ADHF,depending on the time frame and magnitude ofcreatinine level increase. Decreased kidney function also is present as asignificant comorbid condition in approximately 50%of patients with chronic heart failure.
Clinical outcomes in heart failure populations arepoor, and concomitant decreased kidney functionwith eGFR < 60 mL/ min/1.73 m2 significantlyincreases the risk of mortality.
Disorders of the heart and kidneys wherebyacute or chronic dysfunction in one organ mayinduce acute or chronic dysfunction of theother.
● Acute Cardiorenal Syndrome (type 1) Acute worsening of cardiac function leading to decreased kidney function.● Chronic Cardiorenal Syndrome (type 2)Long-term abnormalities in cardiac function leading to decreased kidney function.
● Acute Renocardiac Syndrome (type 3)Acute worsening of kidney function causing cardiac dysfunction.● Chronic Renocardiac Syndrome (type 4)Long-term abnormalities in kidney function leading to cardiac disease.● Secondary Cardiorenal Syndromes (type 5)Systemic conditions causing simultaneous dysfunction of the heart and kidney.
Rapid worsening of cardiac function, leading toacute kidney injury (AKI). Acute heart failure (HF) may be divided into 4subtypes: hypertensive pulmonary edema with preservedleft ventricular (LV) systolic function, acutelydecompensated chronic HF, cardiogenic shock, andpredominant right ventricular failure
In acute HF, AKI appears to be more severe inpatients with impaired LV ejection fraction comparedwith those with preserved LV function, achieving anincidence 70% in patients with cardiogenic shock. Furthermore, impaired renal function (> 0.3 mg/dl )is consistently found as an independent risk factor for 1-year mortality in acute HF patients, including patientswith ST-segment elevation myocardial infarction
A plausible reason for this independent effect mightbe that an acute decline in renal function does not simplyact as a marker of illness severity but also carries anassociated acceleration in cardiovascular pathobiologythrough activation of inflammatory pathways.
In CRS type 1, the early diagnosis of AKIremains a challenge . Classic markers such as creatinine increasewhen AKI is already established and very littlecan be done to prevent it or to protect the kidney.
1- Diuretics and Vasodilators The goal of diuretic use should be to deplete extracellular fluid volume at a rate that allows refilling from the interstitium to the intravascular compartment, recognizing that diuretics potentially aggravate electrolyte imbalances, contract the effective circulating volume, and may contribute to activation of unfavorable neurohormonal responses.
Nitroglycerin is a nitric oxide donor often used torelieve symptoms and improve hemodynamics inpatients with ADHF. At lower doses, it dilates venules, decreases cardiacfilling pressures, and decreases myocardial oxygendemand. At higher doses, it decreases afterload and augmentscardiac output
Sodium nitroprusside acts through cyclic guanosinemonophosphate in vascular smooth muscle to causesignificant arterial and venous vasodilation. As with nitroglycerin, its use often is reserved forpatients with normal or increased blood pressure withevidence of increased preload, afterload, and pulmonaryand venous congestion.
Nesiritide, a recombinant form of human Btypenatriuretic peptide, decreases preload, afterload, andpulmonary vascular resistance; It increases cardiac output in ADHF; and causeseffective diuresis, quickly relieving dyspnea in acuteheart failure states.
A phosphodiesterase inhibitor with lusitropicactivity (calcium sensitizer), improveshemodynamics and renal perfusion and in a smallrandomized trial was found to improve eGFR at72 hours by 45.5%
2- Inotropes In extreme cases of low cardiac output, positive inotropes, such as dobutamine or phosphodiesterase inhibitors, may be required, although their use may accelerate some pathophysiologic mechanisms, increase myocardial injury and arrhythmias, and potentially worsen outcomes.
Characterized by chronic abnormalities in cardiac function (e.g., chronic congestive HF) causing progressive CKD. Worsening renal function in the context of HF is associated with adverse outcomes and prolonged hospitalizations.The prevalence of renal dysfunction in chronic HF has been reported to be approximately 25%
Neurohormonal abnormalities are presentwith excessive production of vasoconstrictivemediators (epinephrine, angiotensin,endothelin) and altered sensitivity and/orrelease of endogenous vasodilatory factors(natriuretic peptides, nitric oxide).
Pharmacotherapies used in the management of HFmay worsen renal function. Diuresis-associated hypovolemia, early introductionof renin-angiotensin aldosterone system blockade, anddrug-induced hypotension have all been suggested ascontributing factors
Recently, there has been increasing interest in thepathogenic role of relative or absolute erythropoietindeficiency contributing to a more pronounced anemiain these patients than might be expected for renalfailure alone. Erythropoietin receptor activation in the heartmay protect it from apoptosis, fibrosis, andinflammation.
Preliminary clinical studies show that erythropoiesisstimulating agents in patients with chronic HF, CKD,and anemia lead to improved cardiac function, reductionin LV size, and the lowering of B-type natriuretic peptide(BNP).
1- RAAS Blockade Blockade of the RAAS is part of the cornerstone of management of patients with heart failure There is evidence of renoprotective effects of ACE inhibitors or angiotensin receptor blockers even with considerably decreased kidney function. Up to a 30% increase in creatinine level that stabilizes within 2 months was associated with improved long-term preservation of kidney function
2- Aldosterone Blockade Spironolactone and eplerenone have improved morbidity and mortality in patients with left ventricular ejection fraction (35%) despite conventional therapy or those with ejection fraction (40%) after acute myocardial infarction.
3- Beta Blockers Has an important role in interrupting the sympathetic nervous system in patients with congestive heart failure and/or ischemic heart disease, and their use generally is considered to be neutral to kidney function.
Certain Beta-blockers may be relativelycontraindicated because of alteredpharmacokinetics, and acute administrationofbeta -blockers in the setting of type 1 CRSgenerally is not advised until hemodynamicstabilization has occurred. Particular concern applies to -blockersexcreted by the kidney, such as atenolol, nadolol,or sotalol.
characterized by an abrupt and primaryworsening of kidney function (e.g., AKI,ischemia, or glomerulonephritis), leading toacute cardiac dysfunction (e.g., HF,arrhythmia, ischemia)
A unique situation leading to type 3 CRS is bilateralrenal artery stenosis (or unilateral stenosis in a solitarykidney). Patients may be prone to acute or decompensated HFbecause of diastolic dysfunction related to chronicincrease of blood pressure from excessive activation ofthe renin-angiotensin-aldosterone axis, renal dysfunctionwith sodium and water retention, and acute myocardialischemia from an increase in myocardial oxygen demandrelated to intense peripheral vasoconstriction.
In these patients, angiotensin blockade isgenerally required to manage the hypertension andHF. However, the GFR is highly dependent uponangiotensin and significant decompensation ofkidney unction may ensue. Patients , those exhibiting renal decompensationwith ACE inhibition or ARB , are likely candidatesfor renal revascularization
The development of AKI can affect the use ofmedications normally prescribed in patients with chronicHF. For example, an increase in serum creatinine from1.5 mg/dl to 2 mg/dl with diuretic therapy and ACEinhibitors, may provoke some clinicians to decrease oreven stop diuretic prescription; they may also decreaseor even temporarily stop ACE inhibitors.
This may, in some cases, lead to acutedecompensation of HF. It should be remembered thatACE inhibitors do not damage the kidney but rathermodify intrarenal hemodynamics and reduce filtrationfraction. They protect the kidney by reducingpathological hyperfiltration. Unless renal function fails to stabilize, or otherdangerous situations arise (i.e., hypotension,hyperkalemia) continued treatment with ACE inhibitorsand ARBs may be feasible.
If AKI is severe and renal replacement therapy isnecessary, cardiovascular instability generated by rapid fluid and electrolyte shifts secondary to conventional dialysis can induce hypotension, arrhythmias, and myocardial ischemia Continuous techniques of renal replacement, which minimize such cardiovascular instability, appear physiologically safer and more logical in this setting.
characterized by a condition of primaryCKD (e.g.,chronic glomerular disease)contributing to decreased cardiac function,ventricular hypertrophy, diastolic dysfunction,and/or increased risk of adverse cardiovascularevents
Individuals with CKD are at extremely highcardiovascular risk . More than 50% of deaths in CKDstage 5 cohorts are attributed to cardiovascular disease. The 2-year mortality rate after myocardial infarctionin patients with CKD stage 5 is estimated to be 50% . Incomparison, the 10-year mortality rate post-infarct forthe general population is 25%.
Troponins Asymmetric Dimethylarginine Plasminogen-activator Inhibitor Type 1 Homocysteine Natriuretic Peptides C-reactive Protein Serum Amyloid A Protein Hemoglobin Ischemia-modified Albumin
The proportion of individuals with CKDreceiving appropriate cardiovascular riskmodification treatment is lower than in the generalpopulation. This leads to treating 50% of patients with CKDwith the combination of aspirin, beta-blockers, ACEinhibitors, and statins Potential reasons for this subtherapeuticperformance include concerns about furtherworsening of renal function, and/or therapy-relatedtoxic effects due to low clearance rates
Characterized by the presence of combinedcardiac and renal dysfunction due to acute orchronic systemic disorders.
There is limited insight into how combinedrenal and cardiovascular failure maydifferentially affect such an outcome comparedto, for example, combined pulmonary and renalfailure
It is clear that several acute and chronic diseasescan affect both organs simultaneously and that thedisease induced in one can affect the other and viceversa. Examples include sepsis, diabetes, amyloidosis,systemic lupus erythematosus, and sarcoidosis.Several chronic conditions such as diabetes andhypertension may contribute to type 2 and 4 CRS.
The various subtypes of CRS present uniquechallenges because therapies directed at one organ mayhave beneficial or detrimental effects on the other. Better understanding of the bidirectional pathwaysby which the heart and kidneys influence each other’sfunction is necessary to tailor therapy appropriate to thesituation.