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Cardio Renal Syndrome CRS All types.pptx
- 2. Case • 18 Months Female Child. • Mother complained of fast breathing since birth. Suck rest suck cycle and feeding diaphoresis present. • Non Syndromic. • ECHO – ACHD/ Inc Qp/ Large Muscular VSD 8mm/ Coarctation of Aorta (Distal to LSCA; ~10mm tight stenosis) – Arch Hypoplasia. • Valves Normal. Lved – 20mm/m2; Posterior Wall – 5mm; EF – 65%; LV hypertrophy.
- 3. Surgery • Trans RA Dacron Patch VSD Closure + Pericardial Patch Aortoplasty. • On 12th of October, 2023. • Aortic Cross Clamp Time : 103 Minutes. • CPB Time : 200 Minutes. • Off Clamp; CHB +.
- 4. Course During ICU Stay. • Upon Shifting : • Peripheral Temp : 31.8 0C • Core Temp : 39.8 0C • Heart Rate : 132 / min on DDD. • RA Pressure : 10 • IBP : 98/76 mmHg on Inf. Dobutamine @10 Mics but stopped after 2 hours of transfer to ICU and Inf. NTG @2 Mics. • Urine Output : 40/20/10. • Drains : Minimal.
- 6. Day 1 • Infusion Milrinone @0.5 Mics started (RV Dysfunction +++); TAPSE 3mm • Sedation Discontinued. • Infusion Albumin + Lasix started @0.3 mg per hour. (Net -83mL) Day 2 • Infusion SNP and NTG tapered off. Milrinone and Lasix Continued. • Net +84 mL. • RV Dysfunction MILD. PASP 45. • Child Extubated.
- 9. Day 3 • Net balance + 47 mL. • TTE – Severe PAH; Severe TR; PASP 70. • Child was reintubated in view of Tachypnoea and Resp Distress. • Inf. Dobutamine restarted. • ~ 8 Hours of Anuria. • Peritoneal Dialysis initiated. • Inf Lasix Stopped.
- 13. EVOLUTION OF DEFINITIONS Cardiorenal Syndrome (CRS) refers to a group of diseases where either the heart or the kidneys are damaged. Understanding how the heart and kidneys interact is crucial for treating these conditions, whether they're acute or chronic. Managing CRS is complex and requires a team of experts who understand the underlying causes. Identifying and understanding the underlying issues in CRS can significantly improve patient outcomes. Working Group of the National Heart, Lung, and Blood Institute in 2004
- 14. EVOLUTION OF DEFINITIONS • Acute Dialysis Quality Initiative in 2008. • Classified CRS into 2 major groups, cardiorenal and renocardiac syndromes, based on the primary cause of the disease process. • This was further grouped into 5 subtypes based on disease acuity and sequential organ involvement
- 15. CLASSIFICATION OF CRS BASED ON THE CONSENSUS CONFERENCE OF THE ACUTE DIALYSIS QUALITY INITIATIVE
- 16. AKI DEFINITION AND STAGING ACCORDING TO KDIGO CRITERIA KIDNEY DISEASE: IMPROVING GLOBAL OUTCOMES
- 17. AKI DEFINITION AND STAGING ACCORDING TO KDIGO CRITERIA KIDNEY DISEASE: IMPROVING GLOBAL OUTCOMES
- 18. CAUSES OF ACUTE KIDNEY INJURY: EXPOSURES AND SUSCEPTIBILITIES FOR NONSPECIFIC ACUTE KIDNEY INJURY
- 19. PATHOPHYSIOLOGICAL MECHANISMS IN CRS • Cardiorenal Syndrome : A condition in which there is a dysfunctional interaction between the heart and the kidneys. • It can be bidirectional. • It can be acute / chronic. • It could be reversible / irreversible. How do the heart and kidneys work together normally? What happens if one fails? What happens if both fail?
- 20. HOW ARE THEY SUPPOSED TO WORK? • Pumps Blood • Perfuse Organs and Tissues • Supply oxygen and nutrients. • Regulate Extracellular Fluid Volume. • Excrete Metabolic Waste Products. • Allows Heart to function with Maximum Efficiency.
- 21. WHAT HAPPENS WHEN HEART DOES NOT WORK? • Pumps Blood • Perfuse Organs and Tissues • Supply oxygen and nutrients. • Regulate Extracellular Fluid Volume. • Excrete Metabolic Waste Products. • Allows Heart to function with Maximum Efficiency. • Decreased CO. • Decreased SV. • Decreased Renal Blood Flow. • Decreased GFR. • Increased Metabolic Waste. • Raised Sodium and Water Reabsorption.
- 22. HEART FAILURE • DECREASED CARDIAC OUTPUT • DECREASED STROKE VOLUME DECREASED EFFECTIVE CIRCULATING VOLUME (BARORECEPTORS) INCREASED RAA INCREASED SNS INCREASED ADH VASOCONSTRICTION; INCREASED SODIUM REABSORPTION. INCREASED WATER REABSORPTION. DECREASED RENAL SODIUM AND WATER EXCRETION. EDEMA INCREASED CAPILLARY HYDROSTATIC PRESSURE INCREASED INTRAVASCULAR VOLUME INCREASED VENOUS PRESSURE
- 23. CRS IN THE ACUTE SETTING CRS-I • Rapid decrease in cardiac function leading to acute kidney injury (AKI). • High CVP = Impaired Glomerular Function. • High RAAS = Detrimental to Kidneys. • Oxidate Stress and Nephrotoxic Drugs CRS - III • AKI, ischemia, or glomerulonephritis leading to acute cardiac impairment. • Higher risk of heart failure, ACS, cerebrovascular disease. CRS – I ACUTE CARDIO RENAL CRS – III ACUTE RENO CARDIAC
- 26. CRS IN THE CHRONIC SETTING CRS- II • Chronic cardiac dysfunction leading to chronic kidney disease (CKD). • Both CKD and heart failure (HF) are chronic inflammatory conditions. • HF with preserved or reduced ejection fraction, AF, and IHD contribute to CRS-2. • TNF-alpha and IL-6 promotes inflammation in the kidneys. • Erythropoietin deficiency. CRS- IV • CKD as the cause of cardiac dysfunction. • CAD and chronic HF common in end-stage renal disease (ESRD) patients. • Fibroblast growth factor-23 (FGF23) progress CKD. CRS – II CHRONIC CARDIO RENAL CRS – IV CHRONIC RENO CARDIAC
- 29. SYSTEMIC CRS • CRS-V • Systemic illness simultaneously damages both the heart and the kidneys. • CRS-V can be classified into four stages based on the disease's pathophysiological process and severity: • hyperacute (0–72 hours), • acute (3–7 days), • subacute (7–30 days), and • chronic (beyond 30 days). • Sepsis, connective tissue diseases like lupus, amyloidosis, sarcoidosis, and cirrhosis. • Complement factors, inflammatory cytokines, RAAS activation. • Septic shock further exacerbates endothelial dysfunction and autoregulation issues.
- 31. BIOMARKERS USEFUL TO SUPPORT THE DIAGNOSIS OF CRS
- 32. BIOMARKERS OF GLOMERULAR FUNCTION • Creatinine and plasma urea levels to calculate estimated glomerular filtration rate (eGFR). • Serum urea = glomerular filtration; tubular reabsorption and neurohormonal activity. • Cystatin C = early stages of acute kidney injury (AKI) • Cystatin-C may be a better diagnostic marker for renal impairment in early AKI compared to creatinine. • Elevated cystatin-C levels ~ coronary artery disease. • Cystatin C, alone or in combination with creatinine, improving risk stratification and the prediction of mortality.
- 33. BIOMARKERS OF TUBULAR FUNCTION • KIM-1 kidney injury molecule-1 = PCT damage; elevated following toxic or ischemic renal injury. • NGAL neutrophil gelatinase-associated lipocalin (lipocalin-2) = Tubular Cells in response to acute tubular damage. • Liver fatty acid-binding protein (L-FABP) marker for tubular function, with higher urine L-FABP concentrations observed in ADHF patients developing AKI.
- 34. URINARY BIOMARKERS • Urinary electrolyte levels and volume. • Early natriuretic response decline is linked to HF. • While 24-hour urine collection-based glomerular filtration rate (GFR). • Creatinine clearance can be employed when GFR predictions based on calculations are uncertain. • Albuminuria serves as a useful tool to assess glomerular integrity.
- 35. CARDIAC BIOMARKERS • Cardiac troponin T (cTnT) - predictive potential - AKI following heart surgery • Subjects who developed AKI had significantly higher cTnT concentrations compared to those without AKI. • Elevated concentrations of natriuretic peptides have relevance in various types of cardiorenal syndrome (CRS). • Copeptin, soluble ST2 (sST2), and Galectin-3 have been explored in the context of cardiac stress, remodeling, and fibrosis in CRS.
- 36. OTHER BIOMARKERS IN CRS PATIENTS • Elevated levels of aldosterone and plasma renin-activity (PRA) are strongly associated with worsening renal function (WRF) in ADHF. • In subjects who experienced myocardial damage from sudden cardiac arrest (SCA), higher levels of cardiac troponin I (TnI), interleukins (IL-1 and IL-10), and endothelin-1 (ET-1) are linked to the development of acute kidney injury (AKI), with IL-6 and ET-1 playing a significant role in the interaction between cardiac and renal impairment in this context.
- 38. CRS IN THE ACUTE SETTING. • In CRS-1, regular kidney function assessment. • Focus on assessing worsening renal function (WRF) onset, causes, diuretic response, and functional status. • Complete decongestion. • Up-titration of diuretic dosage. • Reinitiating and up-titrating RAAS blockers. • Vasodilators for hemodynamically stable ADHF patients, and ultrafiltration – last resort. • The use of vasopressors, inotropes, or mechanical assistance should be evaluated for those with hypotension and inadequate diuretic response.
- 39. • In CRS-3, the treatment approach depends on the cause and severity of acute kidney injury (AKI) and the type of acute cardiac damage. • Loop diuretics. • Renal replacement therapy (RRT) non-recoverable AKI with complications like hyperkalemia, acidemia, and fluid overload. • Negative daily fluid balance with RRT is associated with a better prognosis in subjects with oliguric AKI and critical fluid overload.
- 40. OCCURANCE OF WRF DURING TREATMENT DECONGESTIVE THERAPY IN AHF YES CHECK DIURETIC RESPONSE NO NO WRF CONTINUE DECEONGESTIVE THERAPY TILL DRY GOOD PSEUDO WRF CONTINUE DECEONGESTIVE THERAPY TILL DRY MONITOR CREAT AND ELECTROLYTES RE EVALUATE DECONGESTION DAILY POOR CHECK FOR CONGESTION ABSENT ASSESS CVP CONSIDER TTE MEASURE IAP IF INCREASED IAP; CONSIDER PARACENTESIS PRESENT PSEUDO WRF / WRF MONITOR CREAT AND ELECTROLYTES IF HYPOPERFUSION; CONSIDER INOTROPES; MCS CHECK FOR HYPOPERFUSION AND HYPOTENSION ABSENT INCREASE DIURETIC INTENSITY AND CONSIDER IV VASODILATORS DISCONTINUE / REDUCE BP LOWERING AGENTS AND CONSIDER INOTROPES AND VASOPRESSORS IN CARDIAC OUTPUT IS LOW WRF DUE TO CONGESTION ACHIEVE DECONGESTION. REDUCE DIURETIC DOSE WHEN DRY. RECHECK LABS FREQUENTLY THERAPY RESISTANT WRF. ICU ADMISSION CONSIDER INVASIVE HD GUIDED THERAPY (MCS) CONSIDER ULTRAFILTRATION. WRF DUE TO HYPOPERFUSION / HYPOTENSION. INVASIVE HD MONITORING. ICU ADMISSION RECHECK LABS FREQUNTLY. AVOID HIGH DOSE INOTROPES CONSIDER REDUCING DOSES GDMT IMPROVEMENT NO IMPROVEMENT IMPROVEMENT PRESENT
- 41. OLIGURIA ? ACUTE KIDNEY INJURY (AKI) YES MEASURE URINARY AND SERUM SODIUM; SR. UREA AND SR. CREAT. NO ELIMINATE OFFENDING DRUGS GLUCOCORTICOIDS OTHER RENAL ULTRASONOGRAPHY. URINARY SODIUM <30 mEq/L Sr. UREA/ Sr. CREAT RATIO >20/1 PRE RENAL AKI VOLUME DEPLETION ADMINISTER FLUIDS. AHF. DECONGESTIVE THERAPY HYDRONEPHROSIS BILATERAL SMALL KIDNEYS NORMAL SIZE KIDNEYS POST RENAL AKI REMOVE OBSTRUCTION. PARENCHYMAL DISEASE CKD. URINE ANALYSIS; RENAL BIOPSY INTERSTITIAL NEPHRITIS ACUTE TUBULAR NECROSIS GLOMERULONEPHRITIS AND VASCULITIS ELIMINATE NEPHROTOXINS TREAT UNDERLYING CAUSE IMMUNOSUPPRESSANTS
- 42. CRS IN THE CHRONIC SETTING • OPTIONS : ACEI, ARBs, ARNI, MRA, SGLT2i. • RAAS blockers can decrease GFR in baseline CKD patients. • Sacubitril/valsartan has shown a more favorable impact on GFR reduction compared to enalapril and maintains its positive effects on mortality rates even in individuals with severe CKD. • MRA introduction and SGLT2 inhibitors can also result in an acute decrease in GFR, with SGLT2 inhibitors showing long-term stability in eGFR compared to placebo.
- 43. CHRONIC HEART FAILURE WITH WRF DURING FOLLOWUP YES DURING UPTITRATION OF RAAS INHIBITOR NO NO WRF NO ACTION NEEDED CHECK KFT AND ELECTROLYTES EVERY 4 MONTHS. PRESENCE OF CONGESTION DISCONTINUE RAAS BLOCKERS, CONSIDER OTHER FORMS OF AFTERLOAD REDUCTION HYPER K >5 MEQ/L S.CR >100% INCREASE PSEUDO WRF. TOLERATE CHANGES IN RENAL FUNCITON. CHECK KFT AND ELECTROLYTES EVERY 4 MONTHS. YES S.CR <50% INCREASE + S.CR <3 MG AND GFR STILL >25 ML/MIN YES NO NO YES IMPROVEMENT PSEUDO WRF. CONSIDER RECHALLENGE CONSIDER REDUCING LOOP DIURETIC DOSE. NO YES TREAT CONGESTION TRUE WRF STOP OTHER NEPHROTOXINS. CONSIDER RENAL ARTERY STENOSIS. CONSIDER OTHER CAUSES. NEPHROLOGY CONSULT. NO IMPROVEMENT IMPROVEMENT TRUE WRF DUE TO CONGESTION. ACHIEVE DECONGESTION. REDUCE DIURETICS IF DRY RECHECK LABS FREQUENTLY. CHECK FOR HYPOPERFUSION OR HYPOTENSION. REDUCE DIURETICS / RAASI/ ANTIHYPERTENSIVES. PRESENT TRUE WRF OR INTRINSIC RENAL DISEASE INTRAGLOMERULAR HYPERTENSION CANDIDATE FOR SGLT 2 INHIBITORS NEPHROLOGY CONSULT NO IMPROVEMENT THERAPY RESISTANT WRF. ICU ADMISSION. HD GUIDED THERAPY. CONSIDER MCS AND TRANSPLANT CONSIDER MHD. IMPROVEMENT TRUE WRF. STOP NEPHROTOXINS. CONSIDER CONTINUOUS OR INTERMITTENT INOTROPIC SUPPORT. CONSIDER THERAPIES OF CRT, MCS, TRANSPLANT IF APPROPRIATE. NO
- 45. SYSTEMIC CRS • In CRS-5 - manage the underlying systemic condition. • For septic CRS-5, - eradicating the infection, administering antibiotics, and providing supportive care. • Intravenous fluid management and the use of vasopressors or inotropic medications. • If renal damage persists despite fluid optimization and hemodynamic interventions, renal replacement therapy (RRT) may be recommended as a treatment option.
- 46. CONCLUSION • Understanding the intricate relationship between the heart and the kidney is essential. • Multidisciplinary approach focused on understanding the underlying causes and mechanisms. • Recognizing and characterizing the pathophysiology of CRS. • Comprehensive knowledge of CRS.
- 47. THANK YOU
- 48. CKD is defined as kidney damage or glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) for 3 months or more, irrespective of cause.
Editor's Notes
- Pre op : Urea : 37 and Creat : 0.3 on 7/10/23 Children 1 – 3 years 11 – 36 mg/dL1.8 – 6.0 mmol/L 4 – 13 years 15 – 36 mg/dL 2.5 – 6.0 mmol/L1 4 – 19 years 18 – 45 mg/dL 2.9 – 7.5 mmol/L
- Cardiorenal Syndrome (CRS) refers to a group of diseases where either the heart or the kidneys are damaged. Understanding how the heart and kidneys interact is crucial for treating these conditions, whether they're acute or chronic. Managing CRS is complex and requires a team of experts who understand the underlying causes. Identifying and understanding the underlying issues in CRS can significantly improve patient outcomes.
- To calculate serum creatinine in mg/dl to μmol/L multiply with 88.4. 0.5 sr creat
- To calculate serum creatinine in mg/dl to μmol/L multiply with 88.4. 0.5 sr creat
- There are two types, arterial, and cardiovascular baroreceptors. Arterial baroreceptors are located in high-pressure regions, namely in the aortic arch, and the carotid bodies, whereas cardiovascular baroreceptors are located within the heart's atria, ventricles, and pulmonary vessels.
- Cardiorenal syndrome type 1 (CRS-1) involves a rapid decrease in cardiac function leading to acute kidney injury (AKI). Reduced cardiac output, often due to kidney hypoperfusion, traditionally links with worsening renal function. Increased central venous pressure and congestion contribute to slow blood flow through the kidney, impairing glomerular function and reducing urine production. The renin-angiotensin-aldosterone system (RAAS) plays a role in worsening renal function and heart failure, with increased renin levels leading to detrimental effects on the kidneys. Oxidative stress and nephrotoxic drugs can also impact kidney function in ADHF. Cardiorenal syndrome type 3 (CRS-3) is characterized by a gradual decline in kidney function due to AKI, ischemia, or glomerulonephritis resulting in acute cardiac impairment, leading to a higher risk of heart failure, acute coronary syndrome, cerebrovascular disease, and other complications.
- Pathophysiology of CRS-1. Interaction between heart and kidney in cardiorenal syndrome type 1. ACE-I, angiotensin-converting enzyme inhibitor; ald, aldosterone; ang II, angiotensin II; ANP, atrial natriuretic peptide; BNP, B-type natriuretic peptide; CVP, central venous pressure; GFR, glomerular filtration rate; IAP, intra-abdominal pressure; KIM-1, kidney injury molecule-1; L-FABP, liver-type fatty acid-binding protein; RAAS, renin-angiotensin-aldosterone system; RBF, renal blood flow; SNS, sympathetic nervous system.
- Pathophysiology of CRS-3. Interaction between heart and kidney in cardiorenal syndrome type 3. CO, cardiac output; GRF, glomerular filtration rate; RAAS, renin-angiotensin-aldosterone system; SNS, sympathetic nervous system. Cardiorenal syndrome type 3 (CRS-3) is characterized by a gradual decline in kidney function due to AKI, ischemia, or glomerulonephritis resulting in acute cardiac impairment, leading to a higher risk of heart failure, acute coronary syndrome, cerebrovascular disease, and other complications.
- Cardiorenal syndrome type 2 (CRS-2) is characterized by chronic cardiac dysfunction leading to chronic kidney disease (CKD). Both CKD and heart failure (HF) are chronic inflammatory conditions, resulting in the production of proinflammatory molecules, causing tissue damage, fibrosis, and cell death. CKD is common in chronic HF patients, with a prevalence ranging from 20% to 57%. Various underlying conditions like HF with preserved or reduced ejection fraction, atrial fibrillation, and ischemic heart disease contribute to CRS-2. Oxidative stress and inflammation play a significant role, with molecules like TNF-alpha and IL-6 promoting inflammation in the kidneys. Erythropoietin deficiency, often associated with CKD, has been investigated for its potential role in improving cardiac function. CRS-4 is characterized by CKD as the cause of cardiac dysfunction, with renal dysfunction being an independent risk factor for cardiovascular disease. Ischemic coronary disease and chronic HF are common in end-stage renal disease (ESRD) patients. Various factors, including vasoconstriction, sodium reabsorption, oxidative stress, and activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS), contribute to CRS-4. Additionally, uremic toxins and hormones like fibroblast growth factor-23 (FGF23) have implications in the progression of CKD and its impact on cardiovascular health.
- Pathophysiology of CRS-2. Interaction between heart and kidney in cardiorenal syndrome type 2. ACE-I, angiotensin-converting enzyme inhibitor; ADHF, acute decompensated heart failure; ANP, atrial natriuretic peptide; BNP, B-type natriuretic peptide; CVP, central venous pressure; GFR, glomerular filtration rate; IAP, intra-abdominal pressure; LVH, left ventricular hypertrophy; RBF, renal blood flow; RAAS, reninangiotensin- aldosterone system; SNS, sympathetic nervous system
- Pathophysiology of CRS-4. Interaction between heart and kidney in cardiorenal syndrome type 4. Ca, calcium; EPO, erythropoietin; LVH, left ventricular hypertrophy; PBUTs, protein-bound uremic toxins; Phos, phosphorus; RAAS, renin-angiotensin-aldosterone system; SNS, sympathetic nervous system
- Cardiorenal syndrome type 5 (CRS-5) occurs when a systemic illness simultaneously damages both the heart and the kidneys. CRS-5 can be classified into four stages based on the disease's pathophysiological process and severity: hyperacute (0–72 hours), acute (3–7 days), subacute (7–30 days), and chronic (beyond 30 days). Systemic disorders that may lead to CRS-5 include sepsis, connective tissue diseases like lupus, amyloidosis, sarcoidosis, and cirrhosis. In septic acute kidney injury (AKI), hemodynamic factors and inflammatory markers play a role in the pathophysiology. Complement factors, inflammatory cytokines, and the activation of the renin-angiotensin-aldosterone system (RAAS) are common pathways for renal and cardiac injury in various types of CRS. In sepsis, organ damage can result from increased renal vascular resistance, elevated oxidative stress, and inflammatory cytokines, such as IL-6. Ischemia and inflammatory mediators are major contributors to AKI in septic patients, with septic shock further exacerbating endothelial dysfunction and autoregulation issues.
- Pathophysiology of CRS-5. Interaction between systemic disease, heart and kidney in cardiorenal syndrome type 5. DIC, disseminated intravascular coagulation; LPS, lipopolysaccharide; RAAS, renin-angiotensin-aldosterone system; ROS, reactive oxygen species; SNS, sympathetic nervous system; SVR, system vascular resistance
- Abbreviations: cTnT and cTnI, troponin T and I; ; KIM-1, kidney injury molecule-1; NGAL, neutrophil gelatinase-associated lipocalin L-FABP, liver fatty acid-binding protein; NT-proBNP, N-terminal pro-B-type natriuretic peptide MR-proANP, Mid-regional proatrial natriuretic peptide MRproADM, mid-regional proadrenomedullin;;;; PRA, plasma renin-activity. ET-1, endothelin 1
- In heart failure (HF) diagnosis, creatinine and plasma urea levels are recommended markers to calculate estimated glomerular filtration rate (eGFR). Serum urea is particularly important due to its connection with not only glomerular filtration but also tubular reabsorption and neurohormonal activity. While serum creatinine is the most common marker for glomerular filtration, it has limitations as the tubules can secrete it. To address this, cystatin C has been explored as a marker for early stages of acute kidney injury (AKI) as it is primarily filtered by the glomerulus without significant tubular secretion. Research suggests that cystatin-C may be a better diagnostic marker for renal impairment in early AKI compared to creatinine. Elevated cystatin-C levels have also been associated with serious cardiovascular events in individuals with coronary artery disease. GFR can be calculated using various formulas based on either serum creatinine, cystatin C, or a combination of both, depending on the clinical situation. Cystatin C, alone or in combination with creatinine, has shown promise in improving risk stratification and the prediction of mortality and chronic kidney disease risk.
- KIM-1, kidney injury molecule-1; NGAL, neutrophil gelatinase-associated lipocalin L-FABP, liver fatty acid-binding protein; There is ongoing debate about how to measure tubular function, and various biomarkers have been studied for this purpose. KIM-1 is an indicator for proximal tubule damage in both plasma and urine, elevated following toxic or ischemic renal injury. Plasma KIM-1 levels are notably higher in individuals with AKI undergoing heart surgery compared to those without AKI and healthy controls. NGAL (lipocalin-2) is a peptide secreted from tubular cells in response to acute damage and is a widely investigated biomarker for tubular damage. High urine NGAL levels have been linked to CKD progression in stages 2-4, and its diagnostic potential has been explored in HF patients, where elevated levels were associated with renal abnormalities and the development of WRF in ADHF patients. Liver fatty acid-binding protein (L-FABP) has been proposed as another marker for tubular function, with higher urine L-FABP concentrations observed in ADHF patients developing AKI. It may have predictive value for ESRD progression and the onset of cardiovascular impairment in CKD.
- In the assessment of renal function, various markers are utilized, including those related to glomerular efficiency, glomerular structure, podocyte function, and indicators of tubular function and damage, often tested in urine samples. Measuring urinary electrolyte levels and volume can be a functional way to evaluate tubular function, which is particularly valuable in heart failure (HF). Early natriuretic response decline is linked to HF, contributing to congestion progression. While 24-hour urine collection-based glomerular filtration rate (GFR) measurements are reliable approximations of true GFR in chronic HF with stable renal function, plasma creatinine levels may shift slowly under non-steady state conditions, potentially leading to errors in GFR calculations. Creatinine clearance can be employed when GFR predictions based on calculations are uncertain. Albuminuria serves as a useful tool to assess glomerular integrity, while urinary tubular damage indicators are employed to monitor the development of acute kidney injury (AKI). However, these tubular damage markers do not effectively identify HF patients with a worse prognosis or reduced diuretic response, limiting their use in HF patients.
- The predictive potential of cardiac troponin T (cTnT) for acute kidney injury (AKI) following heart surgery was investigated by Osmar and colleagues. Subjects who developed AKI had significantly higher cTnT concentrations compared to those without AKI. Elevated concentrations of natriuretic peptides (NP), well-established in diagnosing and prognosing heart failure (HF), have relevance in various types of cardiorenal syndrome (CRS). NP, including B-type natriuretic peptide (BNP), are not only elevated in CRS types 1 and 2 but are also relevant in CRS-4 for recognizing acute HF and predicting cardiovascular events. Additionally, markers like copeptin, soluble ST2 (sST2), and Galectin-3 have been explored in the context of cardiac stress, remodeling, and fibrosis in CRS.
- Elevated levels of aldosterone and plasma renin-activity (PRA) are strongly associated with worsening renal function (WRF) in ADHF. In subjects who experienced myocardial damage from sudden cardiac arrest (SCA), higher levels of cardiac troponin I (TnI), interleukins (IL-1 and IL-10), and endothelin-1 (ET-1) are linked to the development of acute kidney injury (AKI), with IL-6 and ET-1 playing a significant role in the interaction between cardiac and renal impairment in this context.
- A worsening renal function (WRF) is defined as an increase ≥0.3 mg/dL in the serum creatinine level compared with the value on admission. In CRS-1, regular kidney function assessments are recommended during acute decompensated heart failure (ADHF), with a focus on assessing worsening renal function (WRF) onset, causes, diuretic response, and functional status. Achieving complete decongestion is vital. Early examination of diuretic response, sodium excretion, and urine volume estimation, as well as up-titration of diuretic dosage, when necessary, is crucial. Reinitiating and up-titrating renin-angiotensin-aldosterone system (RAAS) blockers is suggested for HF patients with reduced ejection fraction when feasible. If diuretic response is weak or functional status deteriorates, reversible factors such as genitourinary blockage or elevated intra-abdominal pressure from ascites should be considered. In CRS-1, vasodilators are recommended for hemodynamically stable ADHF patients, and ultrafiltration should be considered as a last resort for individuals with progressive fluid overload and AKI. The use of vasopressors, inotropes, or mechanical assistance should be evaluated for those with hypotension and inadequate diuretic response.
- In CRS-3, the treatment approach depends on the cause and severity of acute kidney injury (AKI) and the type of acute cardiac damage. Identifying the origin of AKI and addressing potentially reversible factors is essential. Loop diuretics are a cornerstone of treatment for non-oliguric AKI with volume overload, while renal replacement therapy (RRT) may be required for significant, non-recoverable AKI with complications like hyperkalemia, acidemia, and fluid overload. Negative daily fluid balance with RRT is associated with a better prognosis in subjects with oliguric AKI and critical fluid overload. Loop diuretics impact the sodium-potassium-chloride cotransport system at the cellular level, reducing the kidney's water reabsorption capacity. In CRS-3, management involves addressing the underlying causes of acute kidney injury (AKI) and may include measures like treating obstructive uropathy, prerenal causes, or acute glomerulonephritis, as well as optimizing fluid balance and considering renal replacement therapy (RRT) when necessary.
- Mcs = mechanical circulatory support
- In CRS-2 therapy, various medications have been studied, including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), sacubitril/valsartan (ARNI - angiotensin receptor/neprilysin inhibitor), mineralocorticoid antagonists (MRA), and sodium-glucose cotransporter-2 (SGLT2) inhibitors. The use of RAAS blockers, including ACEIs and ARBs, can lead to a decrease in glomerular filtration rate (GFR) in individuals with baseline chronic kidney disease (CKD). This decline is typically reversible, with serum creatinine recovering in the majority of cases. Sacubitril/valsartan has shown a more favorable impact on GFR reduction compared to enalapril and maintains its positive effects on mortality rates even in individuals with severe CKD. MRA introduction and SGLT2 inhibitors can also result in an acute decrease in GFR, with SGLT2 inhibitors showing long-term stability in eGFR compared to placebo. SGLT2 inhibitors impact sodium-hydrogen exchanger 3 (NHE3) in proximal tubular salt reabsorption, leading to afferent arteriole constriction and reduced filtrate, filtration rate, and glomerular pressure. Dapagliflozin and canagliflozin are SGLT- 2 inhibitors with indications for CKD, and only dapagliflozin is indicated for CKD in patients without T2D.
- mineralocorticoid receptor antagonist drugs SpironolactoneVoltage-dependent L-type calcium channeltargetEplerenoneMineralocorticoid receptortarget
- In CRS-5, the primary focus of therapeutic approaches is on managing the underlying systemic condition, as well as addressing both renal and cardiac impairment and their consequences. For septic CRS-5, treatment involves eradicating the infection, administering antibiotics, and providing supportive care. Early interventions, such as intravenous fluid management and the use of vasopressors or inotropic medications, are crucial for reversing myocardial depression and systemic vasodilation, which can lead to improved cardiac output and renal blood perfusion. If renal damage persists despite fluid optimization and hemodynamic interventions, renal replacement therapy (RRT) may be recommended as a treatment option.
- Cardiorenal Syndrome (CRS) encompasses a range of acute and chronic diseases in which either the heart or the kidney can be the primary organ affected. Understanding the intricate relationship between the heart and the kidney is essential for effective management in both chronic and acute conditions of CRS. The complexity and level of awareness needed to provide optimal treatment for individuals with CRS necessitate a multidisciplinary approach focused on understanding the underlying causes and mechanisms. Recognizing and characterizing the pathophysiology of CRS is crucial for improving the prognosis and outcomes in these challenging cases. Comprehensive knowledge of CRS can lead to more effective management and better clinical outcomes for patients with heart and kidney involvement.
- ACR : Albumin to Creatiinine Ratio AER Albumin Excretion Rate.