AKI - Acute Kidney Injury PDF

# AKI - Acute Kidney Injury ## Dr Hussein Mahdi Ahmed Consultant Physician & Nephrologist ## Introduction - Acute kidney injury (AKI) is rapid and usually reversible decline in renal function as evident by rapid decline in GFR over a period of hours to days. - It may occur in patients with previou...

# AKI - Acute Kidney Injury ## Dr Hussein Mahdi Ahmed Consultant Physician & Nephrologist ## Introduction - Acute kidney injury (AKI) is rapid and usually reversible decline in renal function as evident by rapid decline in GFR over a period of hours to days. - It may occur in patients with previously normal renal function or patients with chronic kidney disease. ## Definition Acute kidney injury (AKI) is a clinical syndrome defined by either an abrupt increase in serum creatinine concentration by ≥0.3 mg/dL within 48 hours, a ≥1.5-fold increase in serum creatinine over the prior 7 days, or urine output <0.5 mL/kg/h for 6 hours. Endorsed by KDIGO: only one criterion needs to be present to fulfill the definition It highlights the increased mortality resulting from even small increases in creatinine. ## Limitations of Sr. Creatinine - **Levels affected by:** - Extracellular volume depletion - Decreased kidney blood flow - Age - Sex - Body mass - Nutritional status - **It is not specific for AKI and requires differentiation from other pre-renal or extra-renal causes.** - **It is not specific for renal tubular lesions.** - **Reflect the loss of glomerular filtration function, accompanying the development of AKI.** - **It is a poor marker of kidney dysfunction as changes in its concentrations are neither sensitive nor specific in response to slight GFR alterations and detected later than the actual GFR changes.** ## Definitions of Terminology - **Azotemia:** the accumulation of nitrogenous wastes (high BUN) - **Uremia:** clinical manifestation (symptomatic renal failure) - **Oliguria:** UOP < 400 mL/24 hours - **Anuria:** UOP < 100 mL/24 hours ## Incidence - Incidence of dialysis-dependent AKI: 7200 per million population annually. - 5 - 10% of general hospital admissions. - 20 - 25% of patients with sepsis and ≈ 50% with septic shock. - 50% of all ITU admissions (where it acts as an independent risk factor for mortality of 20 - 60%, depending on AKI stage). - KDIGO estimate a worldwide AKI prevalence of 72,100 per million population, the majority of which are community-acquired. - The burden of AKI may be highest in developing countries. - Individuals with CKD are at increased risk of AKI (and AKI is a risk factor for progression of CKD) ## To function properly kidneys require: - Normal renal blood flow - Prerenal. - Functioning glomeruli, tubules and interstitium - Intrinsic/Renal. - Clear urinary outflow tract - Postrenal. ## Acute or Chronic? Distinguishing between AKI and chronic renal impairment is important, as: - The approach to these patients differs greatly. - This may, save a great deal of unnecessary investigation. ## Definition & Staging of AKI | Stage | Cr criteria | UO criteria | |---|---|---| | 1 | Increase in Cr by ≥26.5 µmol/l within 48hrs OR 50-99% increase in Cr from baseline. Baseline is known or presumed to have occurred within prior 7 days | < 0.5 ml/kg/h for 6-12h | | 2 | 100-199% rise in Cr | < 0.5 ml/kg/h for ≥ 12h | | 3 | ≥ 200% rise in Cr OR Cr rising ≥ 354 OR Initiation of RRT IN pts younger than 18 decrease in eGFR to < 35 ml/min/1.73 m²| < 0.3 ml/kg/h for ≥ 24h OR Anuria for ≥ 12h | ## Risk factors of AKI - eGFR <60 ml/min/1.73m2 or history of AKI - Diabetes - Heart failure, liver disease, Neurological or cognitive impairment - Use of nephrotoxic drugs - Use of iodinated contrast agents within the past week - Symptoms or history of urological obstruction - Sepsis - Age 65years or over ## Causes of AKI A flow chart diagram depicting the causes of AKI. **AKI** - **Prerenal** - Acute GN - ATN - AIN - **Intrinsic** - Acute tubular obstruction - Acute TMA - **Postrenal** **AIN, acute interstitial nephritis; AKI, acute kidney injury; ATN, acute tubular necrosis; GN, glomerulonephritis; TMA, thrombotic microangiopathy** ## Causes | Types | Etiology | Conditions | Examples | |---|---|---|---| | Pre-Renal | Low renal perfusion | Hypovolemia | Diarrhoea, Blood loss, burns (loss of plasma), diuretics, osmotic diuresis, Low fluid intake | | | | Hypoperfusion | Septic shock, Cardiac failure, Hepato renal Syndrome, Impairment of renal autoregulatory responses due to drugs (NSAIDs, ACEI, ARB) Stenosis, Embolism Thrombosis or compression | | Renal | Problem inside kidney | Glomerular obstruction Interstitial Renal tubular Reno-Vascular | Acute Glomerulonephritis Acute Interstitial Nephritis Acute Tubular Necrosis Vasculitis, SLE | | Post Renal | Obstruction to urinary flow | Obstruction | Stones, tumors, Prostatic enlargement(BPH, Malignancy) | ## Causes of AKI in Hospital Setting A pie chart depicts the causes of AKI in a hospital setting. - RPGN - Vascular - Pre-Renal - Acute-on-chronic renal failure - Acute tubular necrosis - Acute interstitial nephritis - Obstruction ## I- Prerenal: (correctable, i.e., normal kidney with ↓ ↓ perfusion) Prerenal AKI is characterized by a decrease in glomerular filtration rate (GFR) in response to impaired renal perfusion with intact renal parenchyma. However, intact tubular function with high urine osmolality and low urine sodium concentrations should not necessarily be interpreted as prerenal AKI, as many intrinsic etiologies, such as glomerulonephritis or AKI due to sepsis, may initially have intact tubular function. ## I- Prerenal: (correctable, i.e., normal kidney with ↓↓ perfusion) | | Decreased effective circulatory volume (Hypovolemia) | Reduced COP | |---|---|---| | 1. | Hemorrhage: Traumatic, surgical, postpartum, gastrointestinal GI). | Diseases of the myocardium, valves, and pericardium; | | 2. | GI fluid loss: Vomiting, diarrhea, surgical drainage. | arrhythmias; | | 3. | Kidney loss: Diuretic therapy, osmotic diuresis in diabetes, and adrenal insufficiency. | massive pulmonary embolism; | | 4. | Vasodilatory loss of the extravascular compartments: Sepsis syndromes, acute pancreatitis, peritonitis, severe trauma, burns, and severe hypoalbuminemia. | positive-pressure mechanical ventilation | ## Pathogenesis of Prerenal Failure Three diagrams describe the pathogenesis of prerenal failure. - **Diagram 1:** The kidneys receive about 25% of the cardiac output at rest. - **Diagram 2:** If cardiac output is reduced or if there is hypovolemia, regional vasoconstriction occurs limiting the blood flow to organs other than the heart and brain. - **Diagram 3:** Initially the blood flow is diminished to the skin then GIT and muscles. Usually, the kidney can maintain GFR close to normal despite wide variations in renal perfusion (autoregulation through VC of efferent). Further decrease of COP or intravascular volume leads to further depression of renal perfusion with drop of glomerular filtration due to selective cortical vasoconstriction → oliguria. ## Acute Tubular Necrosis (ATN) - ATN is one of the most important cause for ARF (Renal cause) - ATN can be produced by ischemia of tubules due to various causes, nephrotoxicity (drugs, infections), transfusion reaction, heavy metal poisoning, septicemias etc. - There are two phases of ATN - **Oliguric phase:** urine output reduces, patient develop fluid overload, oedema, pulmonary oedema, uremia, hyperkaler. - **Diuretic phase:** in this phase, patient passes urine in large amounts due to a defective tubular concentrating capacity ## Pathophysiology of Ischemic Acute Renal Failure A diagram depicts the pathophysiology of ischemic acute renal failure. - **MICROVASCULAR** - Glomerular - ↑ Vasoconstriction in response to: - endothelin, adenosine, angiotensin II, thromboxane A2, leukotrienes, sympathetic nerve activity - Vasodilation in response to: - nitric oxide, PGE2, acetylcholine, bradykinin - ↑ Endothelial and vascular smooth muscle cell structural damage - ↑ Leukocyte-endothelial adhesion, vascular obstruction, leukocyte activation, and inflammation - Medullary - ↑ 02 - **TUBULAR** - Cytoskeletal breakdown - Loss of polarity - Apoptosis and necrosis - Inflammatory and vasoactive mediators - Desquamation of viable and necrotic cells - Tubular obstruction - Backleak - Interacting microvascular and tubular events contributing to the pathophysiology of ischemic acute kidney injury. ## There are 4 phases that can be distinguished in the natural history of AKI 1. **Initiation phase:** This phase presents with normal urine output as it commences from the initial impact of the insult (cause) until the point of actual kidney damage. The duration of this phase is usually several hours and varies depending on the causative factor. 2. **Oliguria (urine output 100-400 mL/d) or anuria (urine output <100 mL/d):** This phase occurs when urine output is typically between 50 and 400 mL/d. It develops in ~50% of patients and lasts an average of 10 to 14 days but can vary from 1 day to 8 weeks 3. **Polyuria:** This phase begins with rapidly increasing urine output over several days after a period of oliguria or anuria. It occurs due to tubular dysfunction and is manifested by sodium wasting and polyuria. Serum creatinine and urea levels may not decrease for several days. The duration of polyuria is proportional to the duration of oliguria/anuria and may last up to several weeks. This phase of AKI is associated with considerable risk of dehydration and severe loss of electrolytes, particularly potassium and calcium. 4. **Recovery phase:** During this phase urine output gradually returns to normal and serum creatinine and urea begin to normalize. It may take up to several months for complete recovery or for a new baseline function to be established. ## Renal / Intrinsic AKI |Glomerular | Tubular | Interstitial | Vascular | |---|---|---|---| | PSGN, SLE, AGN ANCA associated, anti-GBM disease HSP, Cryoglobulinemia, TTP, HUS | ATN Ischemia-50% Toxins -30% | AIN Drug: NSAIDs, antibiotics Infiltrative : lymphoma Granulomatous- Sarcoidosis, TB Infection : APN | Vascular occlusions - Renal artery occlusion - Renal vein thrombosis - Cholesterol emboli | | 5-15% | 70-80% | 8-20% | < 2% | ## Urinalysis in Acute Kidney Injury A diagram depicting the abnormalities seen on urinalysis in AKI **Normal/bland** - Hematuria - RBC casts - proteinuria - WBC - WBC casts **Abnormal sediment** - Eosinophils - RTE cells - Pigmented casts - Crystalluria - Non-albumin proteinuria - Prerenal - Postrenal - Oncotic AKI - Glomerulopathy - Vasculitis - Thrombotic MA - Pyelonephritis - Interstitial nephritis - AIN - Athero-embolic AKI - ATN - Uric acid - Toxins - Drugs - Plasma cell dyscrasia ## Post-renal Urinary Outflow Tract Obstruction A diagram depicting the causes of post-renal obstruction **Intrinsic** - Intra-luminal - Stone, - Blood clots, - Papillary necrosis - Intra-mural - Urethral stricture, - BPH, - Ca prostate, - Bladder tumour, - Radiation fibrosis **Extrinsic** - Pelvic malignancies - Prolapsed uterus - Retroperitoneal fibrosis ## Postrenal AKI - Postrenal AKI includes a variety of disorders characterized by obstruction of the urinary tract. - In neonates and infants, congenital conditions, such as posterior urethral valves and bilateral ureteropelvic junction obstruction, account for the majority of cases of AKI. - Other conditions, such as urolithiasis, tumor (intraabdominal lesion or within the urinary tract), hemorrhagic cystitis, and neurogenic bladder, can cause AKI in older children and adolescents. - In a patient with 2 functioning kidneys, obstruction must be bilateral to result in AKI. - Relief of the obstruction usually results in recovery of renal function, except in patients with associated renal dysplasia or prolonged urinary tract obstruction. ## Diagnostic Evaluation - careful history taking, and physical examination often narrow the differential diagnosis for the cause of AKI. - Prerenal azotemia should be suspected in the setting of vomiting, diarrhea, glycosuria causing polyuria, and several medications including diuretics, NSAIDs, ACE inhibitors, and ARBs. - Physical signs of orthostatic hypotension, tachycardia, reduced jugular venous pressure, decreased skin turgor, and dry mucous membranes are often present in prerenal azotemia. - A history of prostatic disease, nephrolithiasis, or pelvic or paraaortic malignancy would suggest the possibility of postrenal AKI. ## Approach AKI | | Prerenal AKI | Intrinsic AKI | Postrenal AKI | |---|---|---|---| | History | GI loss or bleed Underlying disease : congenital heart disease, nephrotic syndrome | Prolong shock, drug, rhabdomyolysis, TLS: ATN • Hematuria, edema : AGN • Drug: AIN, ATN | Hx of UTI Abnormal voiding pattern | | Physical examination | Sign of dehydration | Volume overload esp ATN/AGN : edema, rales, cardiac gallop | Abdominal mass | ## Laboratory assessment in AKI - Blood : BUN/Cr, electrolyte, Ca, PO4, uric, CBC - Urine: UA, urea, Na, Cr - **FE Na(%) = U Na / S Na *100 U Cr/ S Cr** - Pre-renal: < 1% - ATN: > 2% - **FE Urea(%)= U urea / S urea *100 U Cr/ S Cr** - Pre-renal: < 35% - ATN: > 50% ## Laboratory assessment in AKI | | Prerenal cause | ATN | Postrenal cause | |---|---|---|---| | Urinalysis | Hyaline cast | Granular cast, cellular casts | Hyaline casts | | Urine sp gr | > 1.020 | ~ 1.010 | < 1.010 | | Urine osm (mmol/kg) | > 350 | ~300 | ~300 | | Urine Na (mmol/L) | < 20 | > 30 | > 40 | | FE Na (%) | <1 | > 2 | > 3 | | FE urea (%) | < 35 | > 50 | - | | BUN/Cr ratio | > 20:1 | 10-20:1 | 10-20:1 | | Urine/plasma Cr | > 40 | < 20 | < 20 | | Ultrasound | normal | normal or increased echogenicity with loss of corticomedullary differentiation | dilated pelvis, ureter and/or bladder depending on level of obstruction | ## Laboratory assessment in AKI | | Prerenal | ATN | Intrinsic renal AIN | Postrenal | AGN | |---|---|---|---|---|---| | Urine output | ↓ | ↑/ ↓ | ↓ usually | Variable | ↓ usually | | UA | Normal | Granular casts Pigmenturia Epithelial casts | Pyuria WBC casts Eosinophiluria | Hematuria RBC casts Proteinuria | Unremarkable | | Urine Na, mEq/L (newborn) | < 10 (<20-30) | >30-40 (>30-40) | >30-40 | <10 | Variable | | FENa* (newborn) | <1% (<2.5%) | >2% (>2.5-3.0%) | >2% | <1% | Variable | | Uosm, mosm (newborn) | >400-500 (>350) | <350 (<300) | <350 | >400-500 | Variable | | Other lab | BUN/Cr >20 | | Eosinophilia? C3,C4 ? ANA+, ? ANCA+ | | | | Imaging | | | | US: dilated system | | ## Management of AKI A diagram depicting the management of AKI - **Hypertension** - **Fluid** - **Treatment causes** - **Drugs** - **Dialysis** - **Electrolytes disturbance** - **Nutritions** ## Initial 7 Steps of AKI Management Bundle - Confirm AKI - Assess emergency: Pulmonary oedema, Hyperkalaemia, Acidosis. - Undertake ABCDE - full clinical examination - Stop nephrotoxic drugs - Urine dipstick test and confirm by RME - Biochemistry - Check & repeat. - Renal ultrasound and consider urinary catheter - Urgent senior review ## Management Principles... - Identify the source of infection and treat aggressively keeping dose adjustment. - Minimise indwelling lines - Remove bladder catheter if anuric. - Identify and treat bleeding tendency: - PPI, H2 antagonist, avoid aspirin - transfuse if required ## Optimise nutritional Support - Maintaining adequate nutrition enhances patient survival - Maintain protein intake about 1gm/Kg/Day - Protein intakes of > 1.2 g/kg/ day can dramatically increase azotaemia. ## RRT - Initiate dialysis before uraemic complications set in. - Early RRT improves mortality and recovery . - Specific types of therapy are available for critically ill patients. ## Fluids, Salt - **Fluid management** - **Volume depleted patients:** unless contraindicated, the patient with a clinical history of fluid loss (vomiting and diarrhea), with hypovolemia (hypotension and tachycardia), with oliguria should be administered intravenous fluid therapy to improve the volume status. Crystalloid solutions, such as normal saline, are preferred for initial therapy - **Volume overload patients:** Hypervolemia may be present during initial evaluation or occur due to excessive fluid administration in the setting of impaired ability to excrete sodium and water. In these type of cases maintain fluid intake equal to the volume of the urine output plus 400 to 500 ml (usually < 1 Liter / day). Diuretics(furosemide 40-80 mg) mav be used to relieve hypervolemia among patients with AKI. - **Salt intake 1 to 2 gm / day** - **Diet: Protein restriction - 0.6gm / Kg/day** ## Acute Management - Correct the cause of renal failure - **Hyperkalemia treatment** - IV Calcium gluconate 10% 10 ml over 10 minutes: Calcium directly antagonizes the membrane actions of hyperkalemia,It decreses membrane excitability, while hypocalcemia increases the cardiotoxicity of hyperkalemia The effect begins within minutes but lasts for few minutes (30-60 min), and the dose can be repeated if any change in the ECG is seen after 5–10 min. - Insulin dextrose infusion can Shifting of potassium into the cells: 25 or 50% 100 ml dextrose with 10 units insulin followed by 5% dextrose at 100 ml / hour ( hyperglycemic patients should not be given glucose – only insulin should be used ). Insulin dextrose infusion is the fastest way to lower serum potassium levels. If effective, the plasma K+ concentration will fall by 0.5–1.5 mEq/L in 15–30 min, and the effect will last for 4-6 hours. - Diuretics - Frusemide 80-100 mg IV, It can remove potassium from body - Potassium binders: Cation exchange resins (Oral / Per rectal /Enema Sodium Polystyrene Sulphonate 15 gm TID) which bind potassium in GI Tract and prevents its absorption. - Potassium restricted diet: Avoid fruits /fruit juises,Dialysis in resistant cases ## Dialysis Indications - Fluid overload - Symptoms of uremia - Severe hyperkalemia - Severe metabolic acidosis - Severe hyperphosphatemia (especially if accompanied by hypocalcemia) - Prevention or treatment of tumor lysis syndrome and removal of toxins (ingestions or inborn errors of metabolism) ## Gastrointestinal tract - Liver - Heart - Kidney A diagram depicting the pathophysiology of cardiorenal syndrome. - **Gastrointestinal tract** - Bacterial translocation from the gut - Inflammatory response - Release of proinflammatory cytokines (eg, TNF-α, IL-6, and IL-1B) - **Liver** - Advanced cirrhosis - Portal hypertension - Vasodilator mediators (NO, CO, and endocannabinoids) - Splanchnic arterial vasodilation - ↓ Vascular resistance - Effective arterial hypovolemia + Activation of vasoconstrictor factors - RAAS - SNS - Release of AVP - **Heart** - High-output heart failure - Cirrhotic cardiomyopathy - Hepatocardiorenal syndrome - Cardiac output - **Kidney** - Adrenal insufficiency - Systemic inflammation - Circulatory dysfunction - ↑ Sympathetic hyperactivity - Hepatorenal physiology: - ↑ Renal vasoconstriction - ↓Renal blood flow - ↓GFR - Sustained vasoconstriction - Tubular hypoxia - Acute Kidney Injury ## New diagnostic criteria for hepatorenal syndrome A table depicting the criteria for diagnosis of hepatorenal syndrome. | HRS type | HRS-AKI | HRS-AKD | HRS-CKD | |---|---|---|---| | 1 | ↑sCr ≥0.3 mg/dL within 48h OR ↑sCr ≥1.5-fold from baseline (3 months) sCr ≥1.5 mg/dL (AKI 1b) Neither sCr cutoff at ≥2.5 mg/dL nor 2 weeks timespan required for diagnosis | eGFR <60 mL/min for <3 months ↑sCr <1.5-fold from baseline (3 months) | eGFR <60 mL/min for ≥3 months | ## Hepatorenal syndrome - Prerenal AKI - Fluid challenge & stop diuretics - HRS-AKI - Diagnosis by exclusion - Predictors of non-response - High sCr at treatment initiation - ACLF stage, MELD, Bilirubin - Sepsis - AKI - ATN-AKI - Tubular/structural injury - Proteinuria or hematuria - Urinary biomarkers (e.g. NGAL) - Tubular injury in HRS-AKI? - Postrenal AKI - Ultrasound ## Differential diagnosis & non-response to treatment A diagram depicting the pathophysiology of hepatorenal syndrome. - **Systemic inflammation** - Bacterial translocation, PAMPS & DAMPS - Inflammatory response in liver & kidney - Antibiotics (AB) - SBP prophylaxis with AB may decrease HRS risk - Currently unclear which patients benefit from AB - Albumin - Binding of proinflammatory molecules - Modulation of inflammation - Long-term administration reduces HRS-AKI incidence - **Circulatory dysfunction & renal perfusion** - Decreased renal perfusion & reduced filtration pressure - ↓GFR - ↑ RAAS - ↑ Na+ retention - Albumin - Plasma expansion - Circulatory dysfunction - TIPS (?) - Peripheral arterial & splanchnic vasodilation - ↑ Vasodilating molecules - ↑ Hyperdynamic circulation - ↓MAP - Vasopressors - Terlipressin > Noradrenaline in patients with HRS-AKI and ACLF ## New diagnostic criteria for hepatorenal syndrome - **AKI** - sCr increase ≥0.3 mg/dL within 48h - OR sCr ≥1.5-fold from baseline (3 months) - ↑ < 2-fold sCr <1.5 mg/dL AKI 1a Removal of diuretics and risk factors - Resolution Close follow-up - ↑ < 2-fold sCr >1.5 mg/dL AKI 1b - ↑ 2 to 3-fold sCr ≥ 4 mg/dL AKI 2 - ↑ ≥ 3-fold sCr ≥ 4 mg/dL AKI 3 - Removal of diuretics and risk factors - AND Albumin 1g/kg/day (max. 100g/day) for 2 days - Progression - Response - Non-response - Differential diagnosis +/- urine biomarkers: Meeting criteria for HRS-AKI? -YES - Vasoconstrictors & Albumin* - NO - Individualized treatment for specific AKI subtype - No response - No AKI regression - RRT therapy as needed if LT candidate - Partial response - AKI stage regression - sCr ≥ 0.3 mg/dL above baseline - Individualized treatment - Full response - Return of sCr level within < 0.3 mg/dL of baseline ## Cardiorenal Syndrome (CRS) Types A diagram depicting the types of cardiorenal syndrome (CRS). - **Primary disease** - **Type 1: Acute CRS** Alteration of renal perfusion is the main trigger (in particular when congestive heart failure is present) - **Type 2: Chronic CRS** Renal fibrosis is particularly important in type 2. Also to be considered drug induced renal toxicity and VAD induced renal effects. - **Type 3: Acute RCS** Salt and water, neuro-hormonal and uremia induced dysregulations are the most important aspects. - ** Type 4: Chronic RCS** Hypertension, CKD induced myopathy, chronic hemodialysis and fluids shifts may be in cause. - **Type 5: Secondary CRS** Common pathogenic patterns (i.e. auto-immunity, micro-circulatory dysfunction, cytokine release) - **Secondary disease** ## Cardiorenal syndrome type 1 A diagram depicting the pathophysiology type 1 cardiorenal syndrome. - **Cardiorenal syndrome type 1** - latrogenic cause (diuretics, ACE-I, contrast agents) - Nephrotoxicity - Acute Heart Failure - RAAS activation (renin, ang II, ald) - ↑ SNS activation - Humoral signaling - IAP, CVP, venous congestion - Cardiac Output (CO) - Acute Kidney Injury - Water excretion - Sodium excretion - ↑ Vasoconstriction - Oxidative stress and ↑ Cytokines secretion - Renal pressure gradient - Renal Perfusion - Vasoconstriction - Hypoperfusion - Reduced RBF - Reduced GFR - Necrosis and Apoptosis - Tubular cell toxicity - Decreased 02 delivery - Organ edema - ANP/BNP resistance - Ischemia - Cardiomiopathy - Arrythmia ## Cardiorenal Syndrome (CRS) Types - Ricci Z, Romagnoli S, Ronco C. Cardiorenal Syndrome. Crit Care Clin. 2021;37(2):335-347. - Schematic representation of the five Cardiorenal syndrome (CRS) types according to the organ direction (primary secondary disease) and the time window (acute or chronic). According to this classification, two CRS (acute and chronic), two renocardiac (acute and chronic) syndromes, and one secondary CRS are depicted. - CKD, chronic kidney disease; RCS, renocardiac syndrome; VAD, ventricular assist device.