ARF is frequently encountered in hospitalized patients.A recent multinational multicenter (observational) study estimated prevalence of ARF in critically ill patients as 5.7% of which 2/3 will need renal replacement therapy.Overall mortality increase proportionately to the severity of the injury.Morbidity is a less appreciated consequence of AKI, associated with increased cost of treatment, increased length of stay and increased risk of chronic kidney disease.
Uchino 2005, in a multicenter/multinational observational study providing good detail on the incidence, spectrum, and out- comes of AKI in ICU patientsMedical patients made up the larger proportion @ 59%, 41% surgicalOverall in hospital mortality was 60%Factors impacting on mortality were:Older age (Odds Ratio 1.02/year)Simplified Acute Physiological Score (OR 1.02 per point)Delayed fulfilment of inclusion criteria (OR 1.02 per day between admission and inclusion in study)Mechanical ventilation (OR 2.11)Use of vasopressors and/or inotropes (OR 1.95)Heamatological medical diagnosis as cause of admission (OR 2.7)Sepsis (OR 1.36) though sepsis was the most common contributing factor at an average of around 50%Cardiogenic shock (OR 1.41)Hepatorenal syndrome (OR 1.87)Admission to a specific ICU as compared to a general ICU (OR 1.64)A lower number of ICU beds (OR 0.57 for ICU’s <10 beds compared to those with >30 beds
Acute kidney injury (AKI), previously termed acute renal failure, refers to a sudden decline in kidney function causing disturbances in fluid, electrolyte, and acid– base balance because of a loss in small solute clearance and decreased glomerular filtration rate (GFR).The nomenclature shift to AKI more accurately represents the spectrum of disease from subclinical injury to complete organ failureThe Acute Dialysis Quality Initiative convened in 2002 and proposed the RIFLE classification (risk, injury, failure, loss, end- stage kidney disease) specifically for AKI in critically ill patients
RIFLE criteria define three grades of severity and two outcome classes. The most severe classification met by either criterion should be usedIt describes acute kidney injury as an abrupt (within 48 hours) reduction in kidney function and separates renal dysfunction into categories in terms of the degree of renal insult The degree of renal dysfunction, according to the RIFLE criteria, is determined by the worst value of either urine output or an assessment of the glomerular filtration rate (GFR)The RIFLE criteria also have the ability to predict mortality in both hospitalized patients and the critically ill.
More recently the Acute Kidney Injury Network (AKIN) further modified the RIFLE criteria recognizing that even very small changes in SCr (greater/equal to 0.3 mg/dL) adversely impact clinical outcomeIndividuals who receive RRT are considered to have met the criteria for AKIN stage 3 irrespective of the stage they are in at the time of RRTThe AKIN classification stipulates that the changes in creatinine occur within a 48-hour period and that urinary tract obstruction, or other easily reversible causes of reduced urinary output, be excluded
The cause of AKI in the ICU is commonly “multi-factorial” and frequently develops from a combination of hypovolaemia, sepsis, medications, and hemodynamic perturbations.It is frequently not possible to isolate a single cause, thereby further complicating the search for effective interventions Sepsis is the most common cause of AKI in a general ICU, accounting for up to 50% of casesAKI is common after cardiac surgery, occurring in up to 42% of patients without pre-existing kidney diseaseTrauma associated AKI is multi-factorial (e.g., hemorrhagic shock, abdominal compartment syndrome, rhabdomyolysis) and occurs in up to 31% of adult trauma patientsThe kidneys are early sensors of intra-abdominal hypertension and abdominal compartment pressures >=12 mm Hg may be associated with AKIRhabdomyolysis accounts for 28% of trauma-associated AKI requiring dialysis
Medications are a common cause of AKI and account for nearly 20% of all cases of AKI in the ICUThe mechanism of medication induced AKI is variable and includes acute interstitial nephritis, direct tubular toxicity (e.g., Aminoglycosides)Included on next slide
A list of some medications associated with AKI and illustrates the wide spectrum of possible patterns of injury
-S-creatinine is readily available and continues to be the primary guide for the assessment of renal dysfunction. Factors affecting creatinine include body size, catabolic state, presence of rhabdomyolysis, dilutional effects and drugs-Urea is also affected by many factors but it does correlate with uremic complications-Prediction equations can be used to estimate the glomerular filtration rate (GFR) from s-creatinine. In adults, the most commonly used formulae for estimating GFR are those derived from the Modification of Diet in Renal Disease (MDRD) study population (26) and that by Cockcroft and Gault-MDRD equation for GFR: 170 X SCr-0.999 X age-0.176 X SUN -0.170 XSAlb0.318 (0.762 female) X (1.180 black); Cockroft and Gault equation for GFR: f[(140 – age) X weight]/[72 X SCr (mg/dl)]g X (0.85 if female). SCr = serum creatinine (mg/dl); SUN = serum urea nitrogen (mg/dl); Salb = serum albumin (g/dl)
Cystatin-C is a 13 kD endogenous cysteine-proteinase inhibitor that is produced by all nucleated cells. It mostly reflects a reduction in glomerular filtration rate rather than acting as a marker of renal injury. In the critically ill, a 50% increase in levels of serum cystatin C herald the occurrence of AKI one to two days before serum creatinine levels began to rise.Undergoing evaluation as a biomarker. It is freely filtered across glomerulus, and in contrast to creatinine, it is not secreted by the renal epithelial cellsUrinary neutriphil gelatinase (NGAL).Serum levels rise markedly after epithelial damage and the increase is seen within three hours following ischaemic or nephrotoxic injury. Kidney injury molecule -, KIM -1 is a protein that is over-expressed in cells of the proximal renal tubule after ischaemic or nephrotoxic insults. Interleukin -18is induced in the proximal renal tubule after AKI and appears to be useful in the differentiation of acute tubular necrosis from other types of renal disease, as it is not elevated in chronic kidney disease, urinary tract infection or pre-renal failureHowever serum creatinine remains the primary biomarker (in association with urine output when available) fotr the evaluation of patients with AKI
-Volume resuscitation using a balanced electrolyte solution,(0.9% N/S may give a hyperchloraemic M Ac.) -Avoid Hydroxyethyl Starch (HES) in Sepsis and renal transplant pts-Minimum daily requirements should be crystalloids-Adequate volume loading and use of vasopressors as needed to reach a sufficient mean arterial pressure.-Remark: The optimal fluid resuscitation to prevent AKI is unknown.-A MAP target of at least 65 mm Hg appears appropriate for most patientsThe beneficial effects of tight insulin control remains controversial-2 large RCT have shown a decrease in incidence of AKI & decreased requirement for RRTNICE-SUGAR found an increased mortality in adults under tight control in the ICU setting (no report of the incidence of AKI)These findings warrant further studyAminoglicosides used in gr-ve are associated with significant nephrotoxicityAmpho-B associated with AKI in 25%- 30% of patients - lipid formulation less nephrotoxicMeds must be dose adjustedDiuretics can increase urine output but have not been found to have a consistent impact on mortality. Failure to respond to diuretics was associated with an increased risk of death and non-recovery of renal function. Because diuretic use in AKI has not been shown to decrease mortality, there is no role for diuretics to convert oliguric AKI to nonoliguric AKI.
RRT is a blood purification technique using the principles of diffusion and ultrafiltration.During RRT the concentration of the solute in the blood is altered by exposing the blood to another solution (dialysate) across a semi permeable membrane (filter).Depends on the [ ] gradient, molecular weight, size and resistance of the membraneAnticoagulation is required to prevent clotting in the external dialysis circuit
Continuous venovenoushaemofiltration – CVVH and continuous venovenoushaemodiafiltration – CVVHDare both low-pressure systemsSince there is no arterial component to drive the diffusion roller-pumps are necessary to create flow.Intermittenthaemodialysis IHD The principles employed in intermittent haemodialysis (IHD) are similar to the continuous methods, but the duration of dialysis is shorter (3–4 hours, every 1–2 days) and the dialysate flows are much higher to improve efficiency of clearance. The shorter duration of IHD necessitates large volume removal over short time periods, which may be poorly tolerated in the critically ill.Sustained low efficiency daily dialysis SLEDD -Hybrid technique of IHD thatis applied for about 8 hours a day.As a hybrid technique it has the desirable properties of both IHD and CRRT namely:Low efficiency solute removal compared to IHD, thus minimising disequilibrium Reduced rate of ultrafiltration compared to IHD minimisinghaemodynamic disturbancesSustained treatment to maximise delivered dose of dialysis Less heparin requirements than CRRT Usually performed overnight, minimising the interruptionsto dialysis caused by therapeutic and diagnostic procedures (e.g. theatre visits, radiological interventions)
During dialysis (Left), the solutes diffuse across the membrane that separates the blood from the dialysate. The dialysate flows in the opposite direction to the blood to maximize solute removalDuring haemofiltration (and ultrafiltration, Figure 1b) water is forced across the membrane due to the positive hydrostatic pressure applied to the blood compartment. Solutes are carried along with the fluid by convection. Compared to diffusion (as with dialysis), convection (haemofiltration) removes the larger solutes at a similar rate to the smaller solutesHaemodiafiltration is a combination of dialysis and high volume ultrafiltration.
AKI in the ICU most commonly results from multiple insults. Therefore, appropriate and early identification of patients at risk for AKI provides an opportunity to prevent subsequent renal insults and ultimately impact overall ICU morbidity and mortality
Definitions ARF (AKI) refers to a sudden decline in kidney function AKI more accuratel represents the spectrum/continuum of the disease However more than 35 definitions exist in the literature Acute Dialysis Quality Initiative (www.adqi.net) proposed the RIFLE criteria
Common causes Five Most Common Causes of AKI in the ICU Sepsis (most common) Major surgery Low cardiac output Hypovolaemia Other Common Causes of AKI in the ICU Hepatorenal syndrome, Trauma, Cardiopulmonary bypass, Abdominal compartment syndrome, Rhabdomyolysis
More common causesNSAIDSAntimicrobials Aminoglycosides Amphotericin PenicillinRadio contrast dye IngestionsEthylene glycol
RRT Renal Replacement Therapy (RRT) Blood purification technique using principles of diffusion and ultrafiltration Relies on principle of diffusion Mimic the function and physiology of the kidney Anticoagulation
References Acute kidney injury in the intensive care unit: An update and primer for the intensivist, Paula Dennen, MD; Ivor S. Douglas, MD; Robert Anderson, MD An Official ATS/ERS/ESICM/SCCM/SRLF Statement: Prevention and Management of Acute Renal Failure in the ICU Patient, Laurent Brochard, Fekri Abroug, Matthew Brenner, Alain F. Broccard, Robert L. Danner, Miquel Ferrer, Franco Laghi, Sheldon Magder, Laurent Papazian, Paolo Pelosi, and Kees H. Polderman The critically ill kidney, Piercy JL, SAJAA 2009; 15(3): 21-26 Acute Renal Failure in Critically Ill Patients A Multinational, Multicenter Study Shigehiko Uchino, MD John A. Kellum, MD Rinaldo Bellomo, MD Gordon S. Doig, PhD Hiroshi Morimatsu, MD Stanislao Morgera, MD Miet Schetz, MD Ian Tan, MD Catherine Bouman, MD Ettiene Macedo, MD Noel Gibney, MD Ashita Tolwani, MD Claudio Ronco, MD Acute Dialysis Quality Initiative, www.adqi.net Colloids and crystalloids: does it matter to the kidney? Anthony M. Rochea and Michael F.M. James Acute Kidney Injury in the Intensive Care Unit, Susan T. Crowley, MD, Aldo J. Peixoto, MD